In vivo binding of 2,3,6,2′,3′,6′-hexachlorobiphenyl and 2,4,5,2′,4′,5′-hexachlorobiphenyl to mouse liver macromolecules

Morales, Nydia M.; Matthews, H. B.

doi:10.1016/0009-2797(79)90153-4

Cited by 51 publications

(14 citation statements)

References 17 publications

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“…Covalent binding to cellular macromolecules (adduct formation) has been observed in mice treated with radiolabelled PCB-153 and PCB-136, the binding of the latter decreasing in the order RNA > protein > DNA (Morales & Matthews, 1979). Formation of protein and DNA adducts was observed in vitro with PCB-3 and the tetrachlorinated congeners PCB-47, PCB-49, PCB-52, and PCB-77 (Wyndham et al, 1976;Shimada & Sawabe, 1984).…”

Section: (B) Binding To Dna and Proteinmentioning

confidence: 99%

“…Rodent and human liver microsomes produced similar or different adduct patterns depending on the PCB congener used, indicating that species differences exist. Reactive intermediates can bind to cellular macromolecules, including DNA and DNA-maintenance proteins, and such adducts can be detected in multiple organs (Morales & Matthews, 1979;Amaro et al, 1996;McLean et al, 1996b;Oakley et al, 1996aOakley et al, , 1996bLin et al, 2000;Pereg et al, 2001Pereg et al, , 2002Srinivasan et al, 2002;Arif et al, 2003;Zhao et al, 2004;Bender et al, 2006;Bender & Osheroff, 2007).…”

Section: (Ii) Cell Culture Tests and In-vivo Assaysmentioning

confidence: 99%

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Polychlorinated biphenyls and polybrominated biphenyls

Walker¹

2001

Organic Pollutants

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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 carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in carcinogenesis and related fields; and to indicate where additional research efforts are needed. The lists of IARC evaluations are regularly updated and are available on the Internet at http:// monographs.iarc.fr/.This programme has been supported since 1982 by Cooperative Agreement U01 CA33193 with the United States National Cancer Institute, Department of Health and Human Services. Additional support has been provided since 1986 by the European Commission Directorate-General for Employment, Social Affairs, and Inclusion, initially by the Unit of Health, Safety and Hygiene at Work, and since 2014 by the European Union Programme for Employment and Social Innovation "EaSI" (2014-2020) The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications -whether for sale or for non-commercial distribution -should be addressed to the IARC Communications Group at: publications@iarc.fr.The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.The IARC Monographs Working Group alone is responsible for the views expressed in this publication. IARC Library Cataloguing in Publication Data NOTE TO THE READERThe term 'carcinogenic risk' in the IARC Monographs series is taken to mean that an agent is capable of causing cancer. The Monographs evaluate cancer hazards, despite the historical presence of the word 'risks' in the title.Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a Monograph does not mean that...

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Section: (B) Binding To Dna and Proteinmentioning

confidence: 99%

Section: (Ii) Cell Culture Tests and In-vivo Assaysmentioning

confidence: 99%

Polychlorinated biphenyls and polybrominated biphenyls

Walker¹

2001

Organic Pollutants

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“…A metabolite of 3,3',4,4'-TCB was found to interfere with vitamin A disposition in mouse and rat (Brouwer and van den Berg, 1986). Several studies have indicated the metabolic production of unstable PCB intermediates, which alkylate cellular macromolecules (Hesse et al, 1978;Shimada and Sato, 1978;Hargraves and Allen, 1979;Morales and Matthews, 1979;Shimada and Sato, 1980). The presence of PCB metabolites in tissues may thus render fish susceptible to a range of deleterious effects.…”

Section: Implications Of Tcb Metabolismmentioning

confidence: 99%

“…PCB congeners and mixtures can be metabolically activated to unstable intermediates which alkylate cellular macromolecules (Hesse et al, 1978;Shimada and Sato, 1978;Hargraves and Allen, 1979;Morales and Matthews, 1979;Shimada and Sato, 1980). Some hydroxylated PCB metabolites have inherent toxicity as well.…”

Section: Introductionmentioning

confidence: 99%

Tetrachlorobiphenyl metabolism, toxicity, and regulation of cytochrome P50 expression in a marine teleost fish

White¹

1994

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The effects of 3,3',4,4'-tetrachlorobiphenyl (TCB) were examined in the marine fish scup (Stenotomus chrysops), focusing on the interactions between TCB and the CYP1A1 enzyme system. A low TCB dose (0.1 mg/kg) elicited strong and sustained induction of hepatic CYPlA1 mRNA, protein content, and catalytic activity. A high TCB dose (5.0 mg/kg) elicited similar, strong induction of hepatic CYPlA1 mRNA, but not of CYPlA1 protein content or catalytic activity. This post-transcriptional "suppression" at the high TCB dose was specific for CYPlA1, and was not seen with other hepatic enzymes. In vitro studies indicate that hepatic microsomal CYP A1 is inactivated in the presence of TCB plus cofactor, likely due to the production of reactive oxygen species during TCB occupation of the active site. CYPlA1 inactivation by TCB in vitro may explain the TCBelicited suppression of CYPlA1 protein content in vivo.Both TCB doses elicited strong CYPlA1 induction in vascular endothelium of all organs, which was sustained for several weeks. Induction in intestinal epithelia was stronger at the high TCB dose, but induction in epithelia of liver, kidney, and gill were stronger at the low TCB dose. Both TCB doses caused proliferation of endoplasmic reticulum in liver, renal tubule necrosis, depletion of hematopoietic tissue in kidney, hyperplasia of gill epithelia, and increased number of melanomacrophage aggregates in spleen. The high dose induced tail fin erosion, affecting both epithelial and calcified bone tissue. Tissue alterations were more severe at the high TCB dose, and repair of lesions occurred by day 16 at the low dose. The high dose caused mortality of many individuals.The two TCB congeners 3,3',4,4'-TCB and 2,2',5,5'-TCB were each converted to aqueous-soluble metabolites by hepatic microsomes from scup, beluga whale, and pilot whale. Induction response, correlation analysis, and inhibition studies indicate that 3,3',4,4'-TCB is metabolized by scup CYP1Al, and 2,2',5,5'-TCB by the putative scup CYP2B. Correlation analysis and inhibition studies suggest that 3,3',4,4'-TCB is metabolized by cetacean CYP1A. Both cetacean species expressed microsomal proteins that are immunochemically related to mammalian CYP2B forms. Cytochrome P450 systems from both cetacean species are partially characterized here.

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“…Overwhelming evidence shows that the PCBs are not mutagenic (9). DNA binding has been reported in some crude studies (10), although a specific nucleotide adduct has not been identified (11)(12)(13)(14)(15).…”

Section: Polychlorinated Biphenylsmentioning

confidence: 99%

Understanding Population and Individual Risk Assessment: The Case of Polychlorinated Biphenyls

Shields

2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Decisions about how to improve or protect the public health can be, and sometimes necessarily are, made on imprecise science. The regulation of potential human carcinogens in the environment entails a population-risk assessment process intended to reduce risks to less than one additional cancer in 100,000 or 1,000,000 persons. These risk assessment processes, however, may be miscommunicated or misinterpreted in the context of individual cancer risks by scientists, regulators, the lay media, and the public. This commentary will review methods for establishing a causal relationship between carcinogen exposures and cancer risk. It will use the case of polychlorinated biphenyls (PCB) as an example of how to place scientific data into the context of human exposure and cancer risk. PCBs are widespread environmental contaminants and most people have detectable levels of PCBs in their bodies. The primary source for exposure in the general population is through the diet. PCBs are carcinogens in experimental animal models, but how this information can be extrapolated to human risk remains uncertain. PCB experimental studies provide data that are used to regulate and control human exposure, although the epidemiologic evidence fails to establish PCBs as human carcinogens. Thus, what is used for populationrisk assessment may not be appropriate for individual-risk assessment or concluding that a causal relationship exists between PCB exposure and cancer risk. The hazards from a carcinogen designated by regulatory and review agencies as a ''probable'' human carcinogen is often misunderstood out of context about the magnitude of the risk and in what settings. How scientists communicate their results in scientific articles can strongly influence how others interpret their data. Misunderstandings from both the use of regulatory and review-agency opinions and the conclusions espoused by scientists occur in the media, among private physicians counseling their patients about cancer risk, and in the legal settings where plaintiffs seek compensation for exposure and alleged harm (or future harm). This can lead to false conclusions about what caused a cancer in a specific patient, undue anxiety about future cancer risk, inappropriate cancer screening, and attendant increased morbidity due to increased uses of the medical system and complication rates from medical procedures. The communication of research findings by scientists must be presented with caution, resisting the temptation to extrapolate, inappropriately, research data to the general population. (Cancer Epidemiol Biomarkers Prev 2006;15(5):830 -9)

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In vivo binding of 2,3,6,2′,3′,6′-hexachlorobiphenyl and 2,4,5,2′,4′,5′-hexachlorobiphenyl to mouse liver macromolecules

Cited by 51 publications

References 17 publications

Polychlorinated biphenyls and polybrominated biphenyls

Polychlorinated biphenyls and polybrominated biphenyls

Tetrachlorobiphenyl metabolism, toxicity, and regulation of cytochrome P50 expression in a marine teleost fish

Understanding Population and Individual Risk Assessment: The Case of Polychlorinated Biphenyls

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