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22/10/2009
Pesticide sales and adult male cancer mortality in Brazil
Chrisman JD, Koifman S, de Novaes Sarcinelli P, Moreira JC, Koifman RJ, Meyer A. Int J Hyg Environ Health. Sep 30 2008
Centro de Estudos da Saúde do Trabalhador e Ecologia Humana, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz. Rio de Janeiro, Brazil.
In Brazil, where the use of pesticide grows rapidly, studies that evaluate the impact of pesticide exposure on cancer incidence and mortality are very scarce. In this study, we evaluated the degree of correlation between pesticide sales in 1985 in eleven Brazilian states and cancer mortality rates during 1996-1998. Information of all cancer deaths occurred in men 30-69 years old from 1996 to 1998 were collected from National Mortality System. Single and multiple linear regression coefficients were obtained to assess the relationship between per capita sales of pesticides in 1985, specific-site cancer mortality rates (prostate, soft tissue, larynx, leukemia, lip, esophagus, lung, pancreas, bladder, liver, testis, stomach, brain, non-Hodgkin's lymphoma, and multiple myeloma) during 1996-1998, and several covariates. In addition, states were stratified into three groups according to tertiles of pesticides sales and cancer mortality rate ratios (MRR) were then calculated using first tertile as reference. Finally, a factor analysis was performed to reveal unapparent relationships between pesticide use and cancer mortality. Pesticide sales showed statistically significant correlation with the mortality rates for the cancers of prostate (r=0.69; p=0.019), soft tissue (r=0.71; p=0.015), leukemia (r=0.68; p=0.021), lip (r=0.73; p=0.010), esophagus (r=0.61; p=0.046), and pancreas (r=0.63; p=0.040). Moderate to weak correlations were observed for the cancers of larynx, lung, testis, bladder, liver, stomach, brain, and NHL and multiple myeloma. In addition, correlation between pesticide sales and specific-site cancer mortality rates was reinforced by multiple regression analysis. For all specific-sites, cancer mortality rates were significantly higher in the states of moderate (2nd tertile) and high (3rd tertile) pesticide sales, with MRR ranging from 1.11 to 5.61. Exploring hidden relationships between pesticide sales and cancer mortality in Brazil, through a factor analysis, revealed that affluence; public policies and lifestyle behaviors may explain almost 70% of the variance of the studied association. The results suggest that population exposure to pesticides in the 1980s in some Brazilian States may have been associated with selected cancer sites observed a decade later.
PMID: 18838335
Epidemiological Study of High Cancer among Rural Agricultural Community of Punjab in Northern India
Thakur JS, Rao BT, Rajwanshi A, Parwana HK, Kumar R. Int J Environ Res Public Health. 2008 Dec;5(5):399-407.
School of Public Health, Department of Community Medicine, Post Graduate Institution of Medical Education and Research (PGIMER), Chandigarh-160012, India E-mail: jsthakur64@gmail.com.
Based on a citizen's report, a house-to-house survey was conducted in Talwandi Sabo and Chamkaur Sahib Community Development Blocks in Bathinda and Roop Nagar District respectively in Punjab state located in a northern part of India to identify the number of existing cancer cases, and the number of cancer deaths that occurred in the last 10 years. Age adjusted prevalence of confirmed cancer cases per 100,000 population was 125 (107/85315) in Talwandi Sabo and 72 (71/97928) in Chamkaur Sahib. Cancer of female reproductive system, i.e., breast, uterus/cervix and ovary were more common in Talwandi sabo whereas cancer of blood and lymphatic system, esophagus, and bones were more common in Chamkaur Sahib. Cancer deaths per 100,000 populations per year were 52 in Talwandi Sabo compared to 30 at Chamkaur Sahib. A comparison of the characteristics of randomly selected individuals, from the villages where a cancer case existed or death due to cancer had occurred in last 2 years, revealed that involvement in cultivation, pesticide use, alcohol consumption and smoking were more common in Talwandi Sabo as compared to Chamkaur Sahib. Limited studies show that in drinking water the levels of heavy metals such as As, Cd, Cr, Se, Hg were generally higher, and pesticides such as heptachlor, ethion, and chloropyrifos were also higher in samples of drinking water, vegetables, and blood in Talwandi Sabo as compared to Chamkaur Sahib. As multiple factors were responsible for significantly higher prevalence of cancer cases in Talwandi Sabo, therefore, a multi-pronged strategy to discourage the indiscriminate use of pesticides, tobacco and alcohol needs to be adopted for cancer prevention, and a cancer registry should be set up for elucidation of the role of pesticides and heavy metals in the etiology of cancer in this area.
PMID: 19151435
Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study Cohort.
Andreotti G, Freeman LE, Hou L, Coble J, Rusiecki J, Hoppin JA, Silverman DT, Alavanja MC. Int J Cancer. Nov 26, 2008
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Pancreatic cancer is a rapidly fatal disease that has been linked with pesticide use. Previous studies have reported excess risks of pancreatic cancer with organochlorines such as DDT, however, many other commonly used pesticides have not been examined. To further examine the potential associations between the use of a number of pesticides and pancreatic cancer, we conducted a case-control analysis in the Agricultural Health Study, one of the largest prospective cohorts with over 89,000 participants including pesticide applicators and their spouses in Iowa and North Carolina. This analysis included 93 incident pancreatic cancer cases (64 applicators, 29 spouses) and 82,503 cancer-free controls who completed an enrollment questionnaire providing detailed pesticide use, demographic and lifestyle information. Ever use of 24 pesticides and intensity-weighted lifetime days [(lifetime exposure days) x (exposure intensity score)] of 13 pesticides was assessed. Risk estimates were calculated using unconditional logistic regression controlling for age, smoking, and diabetes. Among pesticide applicators, 2 herbicides (EPTC and pendimethalin) of the 13 pesticides examined for intensity-weighted lifetime use showed a statistically significant exposure-response association with pancreatic cancer. Applicators in the top half of lifetime pendimethalin use had a 3.0-fold (95% CI 1.3-7.2, p-trend = 0.01) risk compared with never users, and those in the top half of lifetime EPTC use had a 2.56-fold (95% CI = 1.1-5.4, p-trend = 0.01) risk compared with never users. Organochlorines were not associated with an excess risk of pancreatic cancer in this study. These findings suggest that herbicides, particularly pendimethalin and EPTC, may be associated with pancreatic cancer. (c) 2008 Wiley-Liss, Inc.
PMID: 19142867
Toward an "omic" physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds
Mass Spectrom Rev. Rubino FM, Pitton M, Di Fabio D, Colombi A. Jan 6, 2009.
Laboratory for Analytical Toxicology and Metabonomics, Department of Medicine, Surgery and Odontology, Università degli Studi di Milano at 'Ospedale San Paolo', v. Antonio di Rudinì 8, Milano I-20142, Italy.
Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors. (c) 2009 Wiley Periodicals, Inc., Mass Spec Rev.
PMID: 19127566
Cancer health effects of pesticides: systematic review.
Bassil KL, Vakil C, Sanborn M, Cole DC, Kaur JS, Kerr KJ.. Can Fam Physician. Oct;53(10):1704-11, 2007
Family Medicine Centre, Queen's University, 220 Bagot St, Kingston, ON. cv4@post.queensu.ca
OBJECTIVE: To review literature documenting associations between pesticide use and cancer. DATA SOURCES: We searched MEDLINE, PreMedline, CancerLit, and LILACS to find studies published between 1992 and 2003 on non-Hodgkin lymphoma, leukemia, and 8 solid-tumour cancers: brain, breast, kidney, lung, ovarian, pancreatic, prostate, and stomach cancer. STUDY SELECTION: Each title and abstract was assessed for relevance; disagreements among reviewers were resolved by consensus. Studies were assessed by a team of 2 trained reviewers and rated based on methodologic quality according to a 5-page assessment tool and a global assessment scale. Studies rated below a global score of 4 out of 7 were excluded. SYNTHESIS: Most studies on non-Hodgkin lymphoma and leukemia showed positive associations with pesticide exposure. Some showed dose-response relationships, and a few were able to identify specific pesticides. Children's and pregnant women's exposure to pesticides was positively associated with the cancers studied in some studies, as was parents' exposure to pesticides at work. Many studies showed positive associations between pesticide exposure and solid tumours. The most consistent associations were found for brain and prostate cancer. An association was also found between kidney cancer in children and their parents' exposure to pesticides at work. These associations were most consistent for high and prolonged exposures. Specific weaknesses and inherent limitations in epidemiologic studies were noted, particularly around ascertaining whether and how much exposure had taken place. CONCLUSION: Our findings support attempts to reduce exposure to pesticides. Reductions are likely best achieved through decreasing pesticide use for cosmetic (non-commercial) purposes (where children might be exposed) and on the job.
PMID: 17934034
Risk assessment and management of occupational exposure to pesticides in agriculture
Maroni M, Fanetti AC, Metruccio F. Med Lav. 2006 Mar-Apr;97(2):430-7
University of Milan, Department of Occupational Health, Hospital L. Sacco, Milano. m.maroni@hsacco.it
Nearly 50% of the world labour force is employed in agriculture. Over the last 50 years, agriculture has deeply changed with a massive utilisation of pesticides and fertilisers to enhance crop protection and production, food quality and food preservation. Pesticides are also increasingly employed for public health purposes and for domestic use. Pesticide are unique chemicals as they are intrinsically toxic for several biological targets, are deliberately spread into the environment, and their toxicity has a limited species selectivity. Pesticide toxicity depends on the compound family and is generally greater for the older compounds; in humans, they are responsible for acute poisonings as well as for long term health effects, including cancer and adverse effects on reproduction. Due to their intrinsic toxicity, in most countries a specific and complex legislation prescribes a thorough risk assessment process for pesticides prior to their entrance to the market (pre-marketing risk assessment). The post-marketing risk assessment takes place during the use of pesticides and aims at assessing the risk for exposed operators. The results of the risk assessment are the base for the health surveillance of exposed workers. Occupational exposure to pesticides in agriculture concerns product distributors, mixers and loaders, applicators, bystanders, and rural workers re-entering the fields shortly after treatment. Assessing and managing the occupational health risks posed by the use of pesticides in agriculture is a complex but essential task for occupational health specialists and toxicologists. In spite of the economic and social importance of agriculture, the health protection of agricultural workforce has been overlooked for too many years, causing an heavy tribute paid in terms of avoidable diseases, human sufferance, and economic losses. Particularly in the developing countries, where agricultural work is one of the predominant job, a sustainable model of development calls for more attention to occupational risks in agriculture. The experience of many countries has shown that prevention of health risk caused by pesticides is technically feasible and economically rewarding for the individuals and the whole community. A proper risk assessment and management of pesticide use is an essential component of this preventative
PMID: 17017381
G-protein-coupled receptor 30 and estrogen receptor-alpha are involved in the proliferative effects induced by atrazine in ovarian cancer cells
Albanito L, Lappano R, Madeo A, Chimento A, Prossnitz ER, Cappello AR, Dolce V, Abonante S, Pezzi V, Maggiolini M. Environ Health Perspect. 2008 Dec;116(12):1648-55
Department of Pharmaco-Biology, University of Calabria, Rende, Italy.
BACKGROUND: Atrazine, one of the most common pesticide contaminants, has been shown to up-regulate aromatase activity in certain estrogen-sensitive tumors without binding or activating the estrogen receptor (ER). Recent investigations have demonstrated that the orphan G-protein-coupled receptor 30 (GPR30), which is structurally unrelated to the ER, mediates rapid actions of 17beta-estradiol and environmental estrogens. OBJECTIVES: Given the ability of atrazine to exert estrogen-like activity in cancer cells, we evaluated the potential of atrazine to signal through GPR30 in stimulating biological responses in cancer cells. METHODS AND RESULTS: Atrazine did not transactivate the endogenous ERalpha in different cancer cell contexts or chimeric proteins encoding the ERalpha and ERbeta hormone-binding domain in gene reporter assays. Moreover, atrazine neither regulated the expression of ERalpha nor stimulated aromatase activity. Interestingly, atrazine induced extracellular signal-regulated kinase (ERK) phosphorylation and the expression of estrogen target genes. Using specific signaling inhibitors and gene silencing, we demonstrated that atrazine stimulated the proliferation of ovarian cancer cells through the GPR30-epidermal growth factor receptor transduction pathway and the involvement of ERalpha. CONCLUSIONS: Our results indicate a novel mechanism through which atrazine may exert relevant biological effects in cancer cells. On the basis of the present data, atrazine should be included among the environmental contaminants potentially able to signal via GPR30 in eliciting estrogenic action.
PMID: 19079715 [PubMed - indexed for MEDLINE]
Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study.
Orsi L, Delabre L, Monnereau A, Delval P, Berthou C, Fenaux P, Marit G, Soubeyran P, Huguet F, Milpied N, Leporrier M, Hemon D, Troussard X, Clavel J.. Occup Environ Med. Nov 18, 2008
Inserm U754, France.
OBJECTIVES: Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LN) in men. METHODS: A hospital-based case-control study was conducted in six centres in France between 2000 and 2004. The cases were incident cases with a diagnosis of lymphoid neoplasm aged 18 to 75 years. During the same period, controls of the same age and gender as the cases were recruited in the same hospital, mainly in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific interviews and case-by-case expert reviews. Four hundred and ninety-one cases (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma (HL), 104 of lymphoproliferative syndromes (LPS) and 56 of multiple myeloma (MM) cases) and 456 controls were included in the analyses. The odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regressions. RESULTS: Positive associations between HL and occupational exposure to triazole fungicides and urea herbicides were observed (OR=8.4 [2.2-32.4], 10.8 [2.4-48.1] respectively). Exposure to insecticides, fungicides and herbicides were linked to a three-fold increases in MM risk (OR=2.8 [1.2-6.5], 3.2 [1.4-7.2], 2.9 [1.3-6.5]). For LPS subtypes, associations restricted to hairy-cell leukaemia (HCL) were evidenced for exposure to organochlorine insecticides, phenoxy herbicides and triazine herbicides (OR=4.9 [1.1-21.2], 4.1 [1.1-15.5], 5.1 [1.4-19.3], although based on small numbers. Lastly, despite the increased odds ratios for organochlorine and organophosphate insecticides, carbamate fungicides and triazine herbicides, no significant associations were evidenced for NHL. CONCLUSIONS: The results, based on case-by-case expert review of occupation-specific questionnaires, support the hypothesis that occupational pesticide exposures may be involved in HL, MM and HCL and do not rule out a role in NHL. The analyses identified specific pesticides that deserve further investigation and the findings were consistent with those of previous studies.
PMID: 19017688
Occupation, exposure to chemicals, sensitizing agents, and risk of multiple myeloma in Sweden. Cancer Epidemiol Biomarkers Prev. Lope V, Pérez-Gómez B, Aragonés N, López-Abente G, Gustavsson P, Plato N, Zock JP, Pollán M. Nov;17(11):3123-7, 2008
CIBER en Epidemiología y Salud Pública, CIBERESP, Spain. vicarvajal@isciii.es
BACKGROUND: This study sought to identify occupations with high incidence of multiple myeloma and to investigate possible excess risk associated with occupational exposure to chemicals and sensitizing agents in Sweden. METHODS: A historical cohort of 2,992,166 workers was followed up (1971--1989) through record linkage with the National Cancer and Death Registries. For each job category, age and period standardized incidence ratios and age and period adjusted relative risks of multiple myeloma were calculated using Poisson models. Exposure to chemicals and to sensitizing agents was also assessed using two job-exposure matrices. Men and women were analyzed separately. RESULTS: During follow-up, 3,127 and 1,282 myelomas were diagnosed in men and women, respectively. In men, excess risk was detected among working proprietors, agricultural, horticultural and forestry enterprisers, bakers and pastry cooks, dental technicians, stone cutters/carvers, and prison/reformatory officials. In women, this excess was observed among attendants in psychiatric care, metal workers, bakers and pastry cooks, and paper/paperboard product workers. Workers, particularly bakers and pastry cooks, exposed to high molecular weight sensitizing agents registered an excess risk of over 40% across the sexes. Occasional, although intense, exposure to pesticides was also associated with risk of myeloma in our cohort. CONCLUSIONS: Our study supports a possible etiologic role for farming and use of pesticides in myeloma risk. The high incidence found in both female and male bakers and pastry cooks has not been described previously. Further research is required to assess the influence of high molecular weight sensitizing agents on risk of multiple myeloma.
PMID: 18990753
Environmental exposures and gene regulation in disease
Edwards TM, Myers JP. etiology. Cien Saude Colet. 2008 Jan-Feb;13(1):269-81
Department of Zoology, University of Florida, Gainesville, FL 32611, USA. tedwards@zoo.ufl.edu
Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. And the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health, and reductions in medical costs, if environmental pollution is decreased.
PMID: 18813540
Environmental and occupational causes of cancer: new evidence 2005-2007
Clapp RW, Jacobs MM, Loechler EL. Rev Environ Health. 2008 Jan-Mar;23(1):1-37.
Boston University School of Public Health, Boston, MA 02118, USA. richard.clapp@gmail.com
What do we currently know about the occupational and environmental causes of cancer? As of 2007, the International Agency for Research on Cancer (IARC) identified 415 known or suspected carcinogens. Cancer arises through an extremely complicated web of multiple causes, and we will likely never know the full range of agents or combinations of agents. We do know that preventing exposure to individual carcinogens prevents the disease. Declines in cancer rates-such as the drop in male lung cancer cases from the reduction in tobacco smoking or the drop in bladder cancer among cohorts of dye workers from the elimination of exposure to specific aromatic amines-provides evidence that preventing cancer is possible when we act on what we know. Although the overall age-adjusted cancer incidence rates in the United States among both men and women have declined in the last decade, the rates of several types of cancers are on the rise; some of which are linked to environmental and occupational exposures. This report chronicles the most recent epidemiologic evidence linking occupational and environmental exposures with cancer. Peer-reviewed scientific studies published from January 2005 to June 2007 were reviewed, supplementing our state-of-the-evidence report published in September 2005. Despite weaknesses in certain individual studies, we consider the evidence linking the increased risk of several types of cancer with specific exposures somewhat strengthened by recent publications, among them brain cancer from exposure to non-ionizing radiation, particularly radiofrequency fields emitted by mobile telephones; breast cancer from exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) before puberty; leukemia from exposure to 1,3-butadiene; lung cancer from exposure to air pollution; non-Hodgkin's lymphoma (NHL) from exposure to pesticides and solvents; and prostate cancer from exposure to pesticides, polyaromatic hydrocarbons (PAHs), and metal working fluids or mineral oils. In addition to NHL and prostate cancer, early findings from the National Institutes of Health Agricultural Health Study suggest that several additional cancers may be linked to a variety of pesticides. Our report also briefly describes the toxicological evidence related to the carcinogenic effect of specific chemicals and mechanisms that are difficult to study in humans, namely exposures to bis-phenol A and epigenetic, trans-generational effects. To underscore the multi-factorial, multi-stage nature of cancer, we also present a technical description of cancer causation summarizing current knowledge in molecular biology. We argue for a new cancer prevention paradigm, one based on an understanding that cancer is ultimately caused by multiple interacting factors rather than a paradigm based on dubious attributable fractions. This new cancer prevention paradigm demands that we limit exposure to avoidable environmental and occupational carcinogens, in combination with additional important risk factors like diet and lifestyle. The research literature related to environmental and occupational causes of cancer is constantly growing, and future updates will be carried out in light of new biological understanding of the mechanisms and new methods for studying exposures in human populations. The current state of knowledge is sufficient to compel us to act on what we know. We repeat the call of ecologist Sandra Steingraber: "From the right to know and the duty to inquire flows the obligation to act."
PMID: 18557596
Linking environmental cancer with occupational epidemiology research: the role of the International Agency for Research on Cancer (IARC)
Goldsmith DF. J Environ Pathol Toxicol Oncol. 2000;19(1-2):171-5
The George Washington University School of Public Health, Washington, DC 20037, USA.
BACKGROUND: The International Agency for Research on Cancer (IARC) provides the most credible assessment of carcinogenicity for the scientific community. IARC Monographs also suggest areas where new laboratory and epidemiology research on cancer should be focused. REVIEW: This presentation examines two recent IARC reports on silica and coal dust (from 1997), and on occupational exposures to insecticide and pesticide applications (from 1991). RESULTS: From the Silica Monograph, the research implications suggest that laboratory and epidemiology studies would be useful focusing on mixtures of hazards where silica is a significant component of the respirable environment: in coal mining (which has an excess of gastric cancers) with variations in silica exposure; in uranium mining where there is silica dust plus radon decay products, in foundries and steel-making plants where silica exposure is common as are other carcinogenic hazards; in agriculture where dusty farming may be common, and comparisons are needed with other polymorphs of silica, including amorphous quartz. Additional studies of lymphatic, dermal, and gastrointestinal malignancies are needed to determine if the evidence of silicocarcinogenesis extends to these tumor sites. Finally, some fundamental studies of adsorptive capability of silica and resultant biologic activity, including biomarker studies, are needed. In the pesticide realm, there are many active ingredients that have been shown to be 2B (or possible) carcinogens based on animal studies (or other evidence). Industrial epidemiology studies of workers manufacturing or handling chemicals such as atrazine, chlordane, dichlorvos, 2,4-D, and DDT should be undertaken. Cancer epidemiology associations have been demonstrated for chemicals such as phenoxy acid herbicides, 2,4,5-T, lindane, methoxychlor, toxaphene, and several organophosphate insecticides for which laboratory studies are needed. CONCLUSIONS: IARC reviews offer many leads for future research and insightful protocols that can provide new leads for studying these common exposures under novel environmental conditions.
PMID: 10905524
Lifestyle-related factors and environmental agents causing cancer: an overview Irigaray P, Newby JA, Clapp R, Hardell L, Howard V, Montagnier L, Epstein S, Belpomme D. Biomed Pharmacother. 2007 Dec;61(10):640-58.
Cancer Research Center, Association for Research and Treatments Against Cancer (ARTAC), 57-59 Rue de la Convention, 75015 Paris, France. philippei.artac@gmail.com
The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed. (1) Over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased in Western Europe and North America. (2) Obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other known lifestyle-related factors. (3) There is evidence that the environment has changed over the time period preceding the recent rise in cancer incidence, and that this change, still continuing, included the accumulation of many new carcinogenic factors in the environment. (4) Genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through gene-environment interactions. (5) Age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children, and adolescents. (6) The fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical time window may explain why current epidemiological studies may still be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment, including microorganisms (viruses, bacteria and parasites), radiations (radioactivity, UV and pulsed electromagnetic fields) and many xenochemicals, may account for the recent growing incidence of cancer and therefore that the risk attributable to environmental carcinogen may be far higher than it is usually agreed. Of major concern are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children and food contamination by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and some ingredients and contaminants in cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.
PMID: 18055160
Environmental and chemical carcinogenesis
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA. Semin Cancer Biol. 2004 Dec;14(6):473-86.
Biological Engineering Division, Massachusetts Institute of Technology, Room 26-009, Cambridge, MA 02139, USA. wogan@mit.edu
People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic or mutagenic properties in experimental systems. Exposure can occur exogenously when these agents are present in food, air or water, and also endogenously when they are products of metabolism or pathophysiologic states such as inflammation. It has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers, when exposures are related to "life-style" factors such as diet, tobacco use, etc. This chapter summarizes several aspects of environmental chemical carcinogenesis that have been extensively studied and illustrates the power of mechanistic investigation combined with molecular epidemiologic approaches in establishing causative linkages between environmental exposures and increased cancer risks. A causative relationship between exposure to aflatoxin, a strongly carcinogenic mold-produced contaminant of dietary staples in Asia and Africa, and elevated risk for primary liver cancer has been demonstrated through the application of well-validated biomarkers in molecular epidemiology. These studies have also identified a striking synergistic interaction between aflatoxin and hepatitis B virus infection in elevating liver cancer risk. Use of tobacco products provides a clear example of cancer causation by a life-style factor involving carcinogen exposure. Tobacco carcinogens and their DNA adducts are central to cancer induction by tobacco products, and the contribution of specific tobacco carcinogens (e.g. PAH and NNK) to tobacco-induced lung cancer, can be evaluated by a weight of evidence approach. Factors considered include presence in tobacco products, carcinogenicity in laboratory animals, human uptake, metabolism and adduct formation, possible role in causing molecular changes in oncogenes or suppressor genes, and other relevant data. This approach can be applied to evaluation of other environmental carcinogens, and the evaluations would be markedly facilitated by prospective epidemiologic studies incorporating phenotypic carcinogen-specific biomarkers. Heterocyclic amines represent an important class of carcinogens in foods. They are mutagens and carcinogens at numerous organ sites in experimental animals, are produced when meats are heated above 180 degrees C for long periods. Four of these compounds can consistently be identified in well-done meat products from the North American diet, and although a causal linkage has not been established, a majority of epidemiology studies have linked consumption of well-done meat products to cancer of the colon, breast and stomach. Studies employing molecular biomarkers suggest that individuals may differ in their susceptibility to these carcinogens, and genetic polymorphisms may contribute to this variability. Heterocyclic amines, like most other chemical carcinogens, are not carcinogenic per se but must be metabolized by a family of cytochrome P450 enzymes to chemically reactive electrophiles prior to reacting with DNA to initiate a carcinogenic response. These same cytochrome P450 enzymes--as well as enzymes that act on the metabolic products of the cytochromes P450 (e.g. glucuronyl transferase, glutathione S-transferase and others)--also metabolize chemicals by inactivation pathways, and the relative amounts of activation and detoxification will determine whether a chemical is carcinogenic. Because both genetic and environmental factors influence the levels of enzymes that metabolically activate and detoxify chemicals, they can also influence carcinogenic risk. Many of the phenotypes of cancer cells can be the result of mutations, i.e., changes in the nucleotide sequence of DNA that accumulate as tumors progress. These can arise as a result of DNA damage or by the incorporation of non-complementary nucleotides during DNA synthetic processes. Based upon the disparity between the infrequency of spontaneous mutations and the large numbers of mutations reported in human tumors, it has been postulated that cancers must exhibit a mutator phenotype, which would represent an early event in cancer progression. A mutator phenotype could be generated by mutations in genes that normally function to guarantee genetic stability. These mutations presumably arise via DNA damage by environmental or endogenous agents, but it remains to be determined whether the acquisition of a mutator phenotype is a necessary event during tumor progression.
PMID: 15489140
Role of xenobiotic metabolic enzymes in cancer epidemiology
Singh MS, Michael M.. Methods Mol Biol. 472:243-64, 2009.
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Victoria, Australia.
The cause of the majority of cancers is poorly understood albeit multifactorial. The ultimate consequence of etiological factors where defined is an alteration within the cellular genotype, which is manifested in the cells acquiring malignant phenotype. There are several environmental carcinogens that contribute to carcinogenesis. These carcinogens are metabolized by a large number of enzymes, including the cyto-chrome P 450 group, glutathione-S-transferase (GST), the uridine glucuronyl transferase (UGT) super-family, alcohol-metabolizing enzymes, sulphatases, etc. These enzymes can either inactivate carcinogens or in some cases generate reactive moieties that lead to carcinogenesis. This review summarises the available evidence regarding the role of xenobiotic metabolic enzymes and their role in cancer epidemiology. The available data and studies have identified correlates between expression of various metabolizing enzymes with risk of malignancies known to be induced by their substrates. The data may have relevance in one population but not for another for a specific malignancy and at times may be conflicting. We believe that with mature data in the future it may be possible to stratify patients by risk.
PMID: 19107436
Review on gene polymorphisms of UDP-glucuronosyltransferases and genetic susceptibility of cancer Wang Y, Zheng Y. Wei Sheng Yan Jiu. 2008 Sep;37(5):629-32.
National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
UDP-glucuronosyltransferases (UGT) are importmant phase II metabolizing enzymes that catalyse the glucuronidation of numerous endobiotics and xenobiotics. Several human hepatic and extrahepatic UGT isozymes have been characterized with respect to their substrate specificity, tissue expression and gene structure. Genetic polymorphisms have been identified for almost all the UGT family members. Some Polymorphisms of UGT gene had an effect on the activity of UGT enzymes, then influenced the glucuronidation against cancer-related substrates, ultimately affected the genetic toxicity and carcinogenesis induced by cancer-related substrates. Numerous studies reported that polymorphisms of UGT gene were associated with the risk of several kinds of cancer, such as colorectal cancer, breast cancer, lung cancer, proximal digestive tract cancer, hepatocellular carcinoma and prostate cancer. This review examines in detail each UGT isozyme known to be associated with cancer.
PMID: 19069670
Persistent organic pollutants and heavy metals in typical seafoods consumed in Singapore
J Toxicol Environ Health A. 2005 Feb 13;68(3):151-66.
Bayen S, Koroleva E, Lee HK, Obbard JP.
Department of Chemistry, National University of Singapore, Singapore. scip0153@nus.edu.sg
In this study, the levels of several heavy metals and persistent organic pollutants (POPs) were measured in the edible portions of 20 different seafood types consumed in Singapore (2 < n < 12). The mean heavy metal concentrations among the seafood types ranged from below detection limits (BLD) to 14.2 microg/g wet weight (ww) for As (shark), to 0.50 microg/g ww for Cd (kunning), to 25.5 microg/g ww for Cu (gray prawn), to 0.58 microg/g ww for Hg (eel), and to 1.21 microg/g ww for Pb (salmon). Chlordane, polychlorinated biphenyls (PCBs), and p, p'-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and its related metabolites (sum noted as DDTs) were the main POPs found among the seafood types, with highest concentrations in salmon fillets and green mussels. Polybrominated diphenyl ether (PBDE) concentrations in salmon fillets (2.75 ng/g ww) were one order of magnitude lower than the highest concentration of PCBs (28.5 ng/g ww). The mean daily intake of contaminants from seafood was calculated for the general population of Singapore. Daily intakes of heavy metals and POPs from seafood are below the oral reference dose set by the U.S. Food and Drug Administration (FDA), except for As, although our study did not characterize the species of As present. Daily intake of As, DDTs, heptachlor, and PCBs in seafood exceeded the conservative cancer benchmark concentrations set by the U.S. Environmental Protection Agency (EPA), suggesting that a significant number of people are potentially at risk in Singapore over a lifetime from seafood consumption.
PMID: 15762177
Persistent organic pollutants and mercury in marine biota of the Canadian Arctic: an overview of spatial and temporal trends
Sci Total Environ. 2005 Dec 1;351-352:4-56. Epub 2005 Aug 16
Braune BM, Outridge PM, Fisk AT, Muir DC, Helm PA, Hobbs K, Hoekstra PF, Kuzyk ZA, Kwan M, Letcher RJ, Lockhart WL, Norstrom RJ, Stern GA, Stirling I.
National Wildlife Research Centre, Canadian Wildlife Service, Environment Canada, Carleton University (Raven Road), Ottawa, ON, Canada K1A 0H3. birgit.braune@ec.gc.ca
This review summarizes and synthesizes the significant amount of data which was generated on mercury (Hg) and persistent organic pollutants (POPs) in Canadian Arctic marine biota since the first Canadian Arctic Contaminants Assessment Report (CACAR) was published in 1997. This recent body of work has led to a better understanding of the current levels and spatial and temporal trends of contaminants in biota, including the marine food species that northern peoples traditionally consume. Compared to other circumpolar countries, concentrations of many organochlorines (OCs) in Canadian Arctic marine biota are generally lower than in the European Arctic and eastern Greenland but are higher than in Alaska, whereas Hg concentrations are substantially higher in Canada than elsewhere. Spatial coverage of OCs in ringed seals, beluga and seabirds remains a strength of the Arctic contaminant data set for Canada. Concentrations of OCs in marine mammals and seabirds remain fairly consistent across the Canadian Arctic although subtle differences from west to east and south to north are found in the proportions of various chemicals. The most significant development since 1997 is improvement in the temporal trend data sets, thanks to the use of archived tissue samples from the 1970s and 1980s, long-term studies using archeological material, as well as the continuation of sampling. These data cover a range of species and chemicals and also include retrospective studies on new chemicals such as polybrominated diphenyl ethers. There is solid evidence in a few species (beluga, polar bear, blue mussels) that Hg at some locations has significantly increased from pre-industrial times to the present; however, the temporal trends of Hg over the past 20-30 years are inconsistent. Some animal populations exhibited significant increases in Hg whereas others did not. Therefore, it is currently not possible to determine if anthropogenic Hg is generally increasing in Canadian Arctic biota. It is also not yet possible to evaluate whether the recent Hg increases observed in some biota may be due solely to increased anthropogenic inputs or are in part the product of environmental change, e.g., climate warming. Concentrations of most "legacy" OCs (PCBs, DDT, etc.) significantly declined in Canadian Arctic biota from the 1970s to the late 1990s, and today are generally less than half the levels of the 1970s, particularly in seabirds and ringed seals. Chlorobenzenes and endosulfan were among the few OCs to show increases during this period while summation operatorHCH remained relatively constant in most species. A suite of new-use chemicals previously unreported in Arctic biota (e.g., polybrominated diphenyl ethers (PBDEs), short chain chlorinated paraffins (SCCPs), polychlorinated naphthalenes (PCNs), perfluoro-octane sulfonic acid (PFOS) and perfluorocarboxylic acids (PFCAs)) has recently been found, but there is insufficient information to assess species differences, spatial patterns or food web dynamics for these compounds. Concentrations of these new chemicals are generally lower than legacy OCs, but there is concern because some are rapidly increasing in concentration (e.g., PBDEs), while others such as PFOS have unique toxicological properties, and some were not expected to be found in the Arctic because of their supposedly low potential for long-range transport. Continuing temporal monitoring of POPs and Hg in a variety of marine biota must be a priority.
PMID: 16109439
Oxidative mechanisms in the toxicity of metal ions
Stohs SJ, Bagchi D. Free Radic Biol Med. 1995 Feb;18(2):321-36
School of Pharmacy, Creighton University, Omaha, NE 68178, USA.
The role of reactive oxygen species, with the subsequent oxidative deterioration of biological macromolecules in the toxicities associated with transition metal ions, is reviewed. Recent studies have shown that metals, including iron, copper, chromium, and vanadium undergo redox cycling, while cadmium, mercury, and nickel, as well as lead, deplete glutathione and protein-bound sulfhydryl groups, resulting in the production of reactive oxygen species as superoxide ion, hydrogen peroxide, and hydroxyl radical. As a consequence, enhanced lipid peroxidation. DNA damage, and altered calcium and sulfhydryl homeostasis occur. Fenton-like reactions may be commonly associated with most membranous fractions including mitochondria, microsomes, and peroxisomes. Phagocytic cells may be another important source of reactive oxygen species in response to metal ions. Furthermore, various studies have suggested that the ability to generate reactive oxygen species by redox cycling quinones and related compounds may require metal ions. Recent studies have suggested that metal ions may enhance the production of tumor necrosis factor alpha (TNF alpha) and activate protein kinase C, as well as induce the production of stress proteins. Thus, some mechanisms associated with the toxicities of metal ions are very similar to the effects produced by many organic xenobiotics. Specific differences in the toxicities of metal ions may be related to differences in solubilities, absorbability, transport, chemical reactivity, and the complexes that are formed within the body. This review summarizes current studies that have been conducted with transition metal ions as well as lead, regarding the production of reactive oxygen species and oxidative tissue damage.
PMID: 7744317
Hazards of heavy metal contamination
Järup L.
Br Med Bull. 2003;68:167-82
Department of Epidemiology and Public Health, Imperial College, London, UK. l.jarup@imperial.ac.uk
The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. These metals have been extensively studied and their effects on human health regularly reviewed by international bodies such as the WHO. Heavy metals have been used by humans for thousands of years. Although several adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues, and is even increasing in some parts of the world, in particular in less developed countries, though emissions have declined in most developed countries over the last 100 years. Cadmium compounds are currently mainly used in re-chargeable nickel-cadmium batteries. Cadmium emissions have increased dramatically during the 20th century, one reason being that cadmium-containing products are rarely re-cycled, but often dumped together with household waste. Cigarette smoking is a major source of cadmium exposure. In non-smokers, food is the most important source of cadmium exposure. Recent data indicate that adverse health effects of cadmium exposure may occur at lower exposure levels than previously anticipated, primarily in the form of kidney damage but possibly also bone effects and fractures. Many individuals in Europe already exceed these exposure levels and the margin is very narrow for large groups. Therefore, measures should be taken to reduce cadmium exposure in the general population in order to minimize the risk of adverse health effects. The general population is primarily exposed to mercury via food, fish being a major source of methyl mercury exposure, and dental amalgam. The general population does not face a significant health risk from methyl mercury, although certain groups with high fish consumption may attain blood levels associated with a low risk of neurological damage to adults. Since there is a risk to the fetus in particular, pregnant women should avoid a high intake of certain fish, such as shark, swordfish and tuna; fish (such as pike, walleye and bass) taken from polluted fresh waters should especially be avoided. There has been a debate on the safety of dental amalgams and claims have been made that mercury from amalgam may cause a variety of diseases. However, there are no studies so far that have been able to show any associations between amalgam fillings and ill health. The general population is exposed to lead from air and food in roughly equal proportions. During the last century, lead emissions to ambient air have caused considerable pollution, mainly due to lead emissions from petrol. Children are particularly susceptible to lead exposure due to high gastrointestinal uptake and the permeable blood-brain barrier. Blood levels in children should be reduced below the levels so far considered acceptable, recent data indicating that there may be neurotoxic effects of lead at lower levels of exposure than previously anticipated. Although lead in petrol has dramatically decreased over the last decades, thereby reducing environmental exposure, phasing out any remaining uses of lead additives in motor fuels should be encouraged. The use of lead-based paints should be abandoned, and lead should not be used in food containers. In particular, the public should be aware of glazed food containers, which may leach lead into food. Exposure to arsenic is mainly via intake of food and drinking water, food being the most important source in most populations. Long-term exposure to arsenic in drinking-water is mainly related to increased risks of skin cancer, but also some other cancers, as well as other skin lesions such as hyperkeratosis and pigmentation changes. Occupational exposure to arsenic, primarily by inhalation, is causally associated with lung cancer. Clear exposure-response relationships and high risks have been observed.
PMID: 14757716
A systematic comparison of the actual, potential, and theoretical health effects of cobalt and chromium exposures from industry and surgical implants
Crit Rev Toxicol. 2008;38(8):645-74
Keegan GM, Learmonth ID, Case CP.
Bristol Implant Research Centre, Department of Clinical Sciences at North Bristol, University of Bristol, Avon Orthopaedic Centre, Southmead Hospital, Bristol, United Kingdom. gemma keegan@hotmail.com
Humans are exposed to cobalt (Co) and chromium (Cr) from industry and surgical devices, most notably orthopedic joint replacements. This review compares the potential health effects of exposure to Co and Cr contaminants from these two different sources, both in the locally exposed tissues and at sites distant to the primary exposure. Surgical implantation results largely in exposures to ions, corrosion products, and particles of Co and Cr. Industrial exposures are predominantly to metal compounds and particles. Although there are large literatures on industrial and surgical exposures to these metals, there has yet to be a systematic comparison of the two to test whether more general lessons might be learned about the human toxicology of Co and Cr. Both industrial and surgical exposures cause inflammatory and other immune reactions in the directly exposed tissues. In the lung there is a well-established risk of cancer following long-term exposures to hexavalent Cr; however, the development of sarcoma in the connective tissues adjacent to implants in response to metal particles is rare. Both types of exposure are associated with changes in the peripheral blood, including evidence of oxidative stress, and altered numbers of circulating immune cells. There is dissemination of Co and Cr to sites distant to the orthopedic implant, but less is known about systemic dissemination of these metals away from the lung. The effects of industrial exposures in the reproductive, renal, and cardiac systems have been investigated, but this has yet to be explored after surgical exposures. The form of the metal (and associated elements) in both instances is key to the toxicological effects arising in the body and further characterization of debris released from devices is certainly recommended, as is the impact of nanotoxicology on the health and safety of workers and patients. Biomonitoring schemes currently used in industry could be translated, if required, into suitable programs for orthopedic out-patients. Cross-communication between experts in industrial and occupational medicine and regulatory agencies may be useful.
PMID: 18720105
Distinctive heavy metal composition of pancreatic juice in patients with pancreatic carcinoma
Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2656-63
Carrigan PE, Hentz JG, Gordon G, Morgan JL, Raimondo M, Anbar AD, Miller LJ.
Department of Molecular Pharmacology and Experimental Therapeutics and Mayo Clinic Cancer Center, Mayo Clinic, Scottsdale, AZ 85259, USA.
Epidemiologic studies have shown the health risks of exposure to cigarette smoke and air pollution, with heavy metal composition implicated as contributing to both. Environmental exposure to cigarette smoke has been epidemiologically associated with pancreatic cancer, but the pathophysiologic basis for this is not yet clear. In the current work, we have used inductively coupled plasma mass spectrometry to quantify the metal composition of pancreatic juice collected in response to secretin stimulation in successive patients evaluated for abdominal pain (35 with pancreatic cancer, 30 with chronic pancreatitis, and 35 with normal pancreas). Indeed, metal composition of pancreatic juice was distinctive in patients with pancreatic cancer relative to those without such a cancer. The metal concentrations that were found to have the strongest association with pancreatic cancer were chromium, selenium, and molybdenum, with 1 SD increases in the concentrations of each associated with substantial increases in the odds of having pancreatic cancer relative to those in patients with normal pancreas (210%, 160%, and 76%, respectively). Of note, elevations in concentrations of chromium and selenium did not correlate in individuals, whereas those having a 1 SD increase in the sum of the concentrations of these two metals in their pancreatic juice had a 480% increase in the odds of having pancreatic cancer. Elevations of nickel and zinc correlated with elevated chromium in individuals, with each of these metals known to be present in cigarette smoke, whereas other recognized metal components of cigarette smoke were not elevated. An understanding of why these metals are elevated in pancreatic juice and what effects they might have on pancreatic cells may have important implications for the diagnosis, treatment, and even prevention of pancreatic cancer.
PMID: 18086771 [PubMed - indexed for MEDLINE
Molecular mechanism involved in chromium(VI) toxicity
Yakugaku Zasshi. 2007 Dec;127(12):1957-65
Kimura T.
Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata City 573-0101, Japan. tomoki@setsunan.ac.jp
Chromium exists in many different oxidation states in the environment, Cr(VI) and Cr(III) being the most stable forms. Chromium has been known for over 100 years to be a human carcinogen. The greatest risk of cancer from chromium exposure is associated with Cr(VI). Cr(VI) enters cells via the sulfate anion transporter system and is reduced to intermediate oxidation states, such as Cr(V) and Cr(IV), in the process of forming stable Cr(III) forms. It is known that Cr(VI) affects expression of various genes. Metal responsive element-binding transcription factor-1 (MTF-1) is involved in sensing heavy metal load and the induced transcription of several protective genes, including metallothionein (MT)-I, MT-II, zinc transporter-1, and gamma-glutamylcysteine synthetase. Cr(VI) inhibits zinc-induced MT transcription via modifying transactivation potential of MTF-1. However, the molecular mechanism for the Cr(VI)-mediated inhibition of MTF-1 has not been fully elucidated. In this review, I briefly summarize the previous studies and discuss the current status of research on Cr(VI) toxicity and Cr(VI)-mediated inhibition against transcription.
PMID: 18057785
Increased levels of transition metals in breast cancer tissue
Neuro Endocrinol Lett. 2006 Dec;27 Suppl 1:36-9
Ionescu JG, Novotny J, Stejskal V, Lätsch A, Blaurock-Busch E, Eisenmann-Klein M.
Research Department of Spezialklinik Neukirchen, Neukirchen, Germany. info@spezialklinik-neukirchen.de
OBJECTIVES: High levels of transition metals such as iron, nickel, chromium, copper, and lead are closely related to free radical generation, lipid peroxidation, formation of DNA strand breaks, and tumor growth in cellular systems. In order to determine the correlation to malignant growth in humans, we investigated the accumulation of heavy metals in 20 breast cancer biopsies and compared the findings to the levels found in 8 healthy biopsies. METHODS: The concentration of transition metals in breast cancer and control biopsies was assessed by a standardized Atomic Absorption Spectrofotometry technique with acidic hydrolysis for sample preparation. Additionally, heavy metal analysis in control biopsies was also performed with an Inductive Coupled Plasma--Mass Spectroscopy technique. For statistical analysis of the results, the Mann-Whitney U Test was applied. RESULTS: A highly significant accumulation of iron (p<0.0001), nickel (p<0.00005), chromium (p<0.00005), zinc (p<0.00001), cadmium (p<0.005), mercury (p<0.005), and lead (p< 0.05) was found in the cancer samples when compared to the control group. Copper and silver showed no significant differences to the control group, whereas tin, gold, and palladium were not detectable in any biopsies. CONCLUSIONS: The data suggest that pathological accumulation of transition metals in breast tissue may be closely related to the malignant growth process.
PMID: 16804515
Hazards of heavy metal contamination
Br Med Bull. 2003;68:167-82
Järup L.
Department of Epidemiology and Public Health, Imperial College, London, UK. l.jarup@imperial.ac.uk
The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. These metals have been extensively studied and their effects on human health regularly reviewed by international bodies such as the WHO. Heavy metals have been used by humans for thousands of years. Although several adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues, and is even increasing in some parts of the world, in particular in less developed countries, though emissions have declined in most developed countries over the last 100 years. Cadmium compounds are currently mainly used in re-chargeable nickel-cadmium batteries. Cadmium emissions have increased dramatically during the 20th century, one reason being that cadmium-containing products are rarely re-cycled, but often dumped together with household waste. Cigarette smoking is a major source of cadmium exposure. In non-smokers, food is the most important source of cadmium exposure. Recent data indicate that adverse health effects of cadmium exposure may occur at lower exposure levels than previously anticipated, primarily in the form of kidney damage but possibly also bone effects and fractures. Many individuals in Europe already exceed these exposure levels and the margin is very narrow for large groups. Therefore, measures should be taken to reduce cadmium exposure in the general population in order to minimize the risk of adverse health effects. The general population is primarily exposed to mercury via food, fish being a major source of methyl mercury exposure, and dental amalgam. The general population does not face a significant health risk from methyl mercury, although certain groups with high fish consumption may attain blood levels associated with a low risk of neurological damage to adults. Since there is a risk to the fetus in particular, pregnant women should avoid a high intake of certain fish, such as shark, swordfish and tuna; fish (such as pike, walleye and bass) taken from polluted fresh waters should especially be avoided. There has been a debate on the safety of dental amalgams and claims have been made that mercury from amalgam may cause a variety of diseases. However, there are no studies so far that have been able to show any associations between amalgam fillings and ill health. The general population is exposed to lead from air and food in roughly equal proportions. During the last century, lead emissions to ambient air have caused considerable pollution, mainly due to lead emissions from petrol. Children are particularly susceptible to lead exposure due to high gastrointestinal uptake and the permeable blood-brain barrier. Blood levels in children should be reduced below the levels so far considered acceptable, recent data indicating that there may be neurotoxic effects of lead at lower levels of exposure than previously anticipated. Although lead in petrol has dramatically decreased over the last decades, thereby reducing environmental exposure, phasing out any remaining uses of lead additives in motor fuels should be encouraged. The use of lead-based paints should be abandoned, and lead should not be used in food containers. In particular, the public should be aware of glazed food containers, which may leach lead into food. Exposure to arsenic is mainly via intake of food and drinking water, food being the most important source in most populations. Long-term exposure to arsenic in drinking-water is mainly related to increased risks of skin cancer, but also some other cancers, as well as other skin lesions such as hyperkeratosis and pigmentation changes. Occupational exposure to arsenic, primarily by inhalation, is causally associated with lung cancer. Clear exposure-response relationships and high risks have been observed.
PMID: 14757716
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