Polychlorinated Biphenyls and Polybrominated Biphenyls

Agudo, Antonio; Aronson, Kristan J.; Bonefeld-Jörgensen, Eva Cecilie; Cocco, Pierluigi; Cogliano, Vincent; Cravedi, Jean Pierre; Esch, Harald; Fiedler, Heidelore; Glauert, Howard P.; Guo, Yueliang Leon; Herbert, Ronald A.; Hopf, Nancy B.; James, Margaret O.; Johansson, Niklas; Bizek, Bruno Le; Ludewig, Gabriele; Machala, Miroslav; Merletti, Franco; Narbonne, Jean‐François; Robertson, Larry W.; Ruder, Avima M.; Tryphonas, Helen; Vermeulen, Roel; Vorkamp, Katrin; Walker, Nigel J.; Carpenter, David O.

doi:10.1201/9781420062595.ch6

Organic Pollutants 2008

DOI: 10.1201/9781420062595.ch6

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Polychlorinated Biphenyls and Polybrominated Biphenyls

Antonio Agudo

Kristan J. Aronson²,

Eva Cecilie Bonefeld-Jörgensen³

et al.

Abstract: initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, lifestyle factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on c… Show more

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Cited by 34 publications

References 412 publications

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Persistent organic pollutants and risk of cutaneous malignant melanoma among women

Darvishian¹,

Bhatti²,

Gaudreau

et al. 2021

Cancer Reports

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Background Despite the increasing trend of cutaneous malignant melanoma (CMM) incidence in Canada, especially among females, few risk factors other than ultraviolet radiation exposure, have been identified. Aim We conducted a case–control study of 406 CMM cases and 181 controls to evaluate the potential impact of body burdens of various persistent organic pollutants on CMM risk. Methods Detailed data on potential confounding factors, including lifetime repeated sun exposure and skin reaction to repeated sun exposure, were collected. Gas chromatography tandem mass spectrometry was used to assay plasma levels of 14 polychlorinated biphenyl (PCB) congeners and 11 organochlorine (OC) pesticides among cases and controls. Results Statistically significant trends of increased CMM risk were observed with increasing plasma concentrations of multiple PCB congeners, including PCBs 138, 153, 170, 180, 183 and 187. For example, compared to lowest plasma concentration quartile of PCB‐138, the second, third and fourth quartiles were associated with 1.7 (95% CI: 0.9–2.9), 2.3 (95% CI: 1.3–4.1) and 2.4 (95% CI: 1.3–4.5) ‐fold increased risks of CMM, respectively. Similarly, increasing plasma concentrations of several OC pesticides (i.e., β‐HCH, HCB, Mirex, oxychlordane and trans‐Nonachlor) showed statistically significant trends with increased CMM risk. For example, compared to lowest plasma concentration quartile of β‐HCH, the second, third and fourth quartiles were associated with 1.3 (95% CI: 0.7–2.3), 2.1 (95% CI: 1.2–3.7) and 2.3 (95% CI: 1.2–4.4) ‐fold increased risks of CMM, respectively. Conclusion Plasma levels of several persistent organic pollutants were highly correlated, suggesting that observed associations were not necessarily independent of each other. Given the highly correlated nature of exposure to PCB and OC analytes, sophisticated analyses that consider complex mixtures should be considered in future studies.

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Persistent organic pollutants and risk of cutaneous malignant melanoma among women

Darvishian¹,

Bhatti²,

Gaudreau

et al. 2021

Cancer Reports

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Hepatic DNA damage in harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines

Acevedo‐Whitehouse

Cole

Phillips

et al. 2018

Environ and Mol Mutagen

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One level at which persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons PAHs) can exert damage is by causing DNA strand‐breaks or nucleotide base modifications, which, if unrepaired, can lead to embryonic mutations, abnormal development and cancer. In marine ecosystems, genotoxicity is expected to be particularly strong in long‐lived apex predators due to pollutant bioaccumulation. We conducted 32P‐postlabeling analyses optimized for the detection and quantification of aromatic/hydrophobic DNA adducts in the livers of 40 sexually‐mature North Atlantic harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines. We examined hepatic tissue to search for inflammatory and preneoplastic lesions and examine their association with adduct levels. Adducts were found in all porpoises (mean: 17.56 ± 11.95 per 108 nucleotides), and were higher than levels reported for marine vertebrates from polluted sites. The pollutants causing the induced DNA adducts could not be further characterized. Hepatic DNA damage did not correlate with levels of blubber POP concentrations (including total polychlorinated biphenyl [PCBs], dichlorodiphenyltrichloroethane [DDT] and dieldrin); PAH concentrations were not available for the present study. However, DNA damage predicted occurrence of inflammatory and preneoplastic lesions. Further, our data showed a reduction in hepatic DNA adduct levels with age in the 40 animals examined while POP concentrations, particularly PCBs, increased with age. Using a different dataset of 145 mature male harbour porpoises confirmed that higher contaminant levels (total PCBs, DDT and dieldrin) are found in older animals. The reduction in hepatic DNA adduct levels in older animals was in accordance with other studies which show that suppression of hepatic CYP1A enzyme activity at high PCB concentrations might impact on CYP1A‐mediated DNA adduct formation of PAHs which are ubiquitous environmental pollutants and readily metabolized by CYP1A to species binding to DNA. In summary, our study shows that pollutant‐induced DNA damage is prevalent in harbour porpoises from UK waters and may lead to detectable sub‐lethal hepatic damage. Environ. Mol. Mutagen. 59:613–624, 2018. © 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society

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Role of RNA modifications in carcinogenesis and carcinogen damage response

Verghese

Wilkinson

2022

Molecular Carcinogenesis

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The field of epitranscriptomics encompasses the study of post-transcriptional RNA modifications and their regulatory enzymes. Among the numerous RNA modifications, N 6 -methyladenosine (m 6 A) has been identified as the most common internal modification of messenger RNA (mRNA). Although m 6 A modifications were first discovered in the 1970s, advances in technology have revived interest in this field, driving an abundance of research into the role of RNA modifications in various biological processes, including cancer. As analogs to epigenetic modifications, RNA modifications also play an important role in carcinogenesis by regulating gene expression post-transcriptionally. A growing body of evidence suggests that carcinogens can modulate RNA modifications to alter the expression of oncogenes or tumor suppressors during cellular transformation. Additionally, the expression and activity of the enzymes that regulate RNA modifications can be dysregulated and contribute to carcinogenesis, making these enzymes promising targets of drug discovery. Here we summarize the roles of RNA modifications during carcinogenesis induced by exposure to various environmental carcinogens, with a main focus on the roles of the most widely studied m 6 A mRNA methylation.

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Polychlorinated Biphenyls and Polybrominated Biphenyls

Cited by 34 publications

References 412 publications

Persistent organic pollutants and risk of cutaneous malignant melanoma among women

Persistent organic pollutants and risk of cutaneous malignant melanoma among women

Hepatic DNA damage in harbour porpoises (Phocoena phocoena) stranded along the English and Welsh coastlines

Role of RNA modifications in carcinogenesis and carcinogen damage response

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