The emperor wears no clothes in the field of carcinogen risk assessment: ignored concepts in cancer risk assessment

The following is a position paper challenging the paradigm that ‘carcinogen = mutagen’, and that the current rodent bioassay to predict risks to human cancers is relevant and useful. Specifically, we review current observations concerning carcinogenesis that might lead to another approach for assess...

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Published in:Mutagenesis Vol. 20; no. 2; pp. 81 - 92
Main Authors: Trosko, James E., Upham, Brad L.
Format: Journal Article
Language:English
Published: England Oxford University Press 01-03-2005
Oxford Publishing Limited (England)
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Summary:The following is a position paper challenging the paradigm that ‘carcinogen = mutagen’, and that the current rodent bioassay to predict risks to human cancers is relevant and useful. Specifically, we review current observations concerning carcinogenesis that might lead to another approach for assessing the identification of human carcinogenic hazards and the risk assessment that chemicals might pose. We give a brief review of the multistage and multimechanism process of cancer in a tissue that involves not only genotoxic but also epigenetic events, and the importance of stem and progenitor cells in the development of cancer. We focus on the often ignored ‘epigenetic’ effects of carcinogens and the role of cell communication systems in epigenetically altering gene expression that leads to an imbalance of cell proliferation, differentiation and apoptosis in a tissue that can contribute to the cancer process. To draw attention to the fact that the current paradigm and policy to test toxic chemicals is often misleading and incorrect, we discuss how oxidative stress, in spite of the DNA damaging data, most probably contributes to cancer at the epigenetic level. Additionally, we briefly review how this mutagenic concept has greatly diverted attention away from doing research on the lower molecular weight, non-genotoxic, polycyclic aromatic hydrocarbons (PAHs), and how these low molecular weight PAHs are etiologically more relevant to the disease potential of environmental mixtures such as cigarette smoke.
Bibliography:local:gei017
istex:40A2333FF2A62A4C65981E701CE6CC6861DFC381
To whom correspondence should be addressed. Tel: +1 517 432 3100, Ext. 188; Fax: +1 517 432 6340; Email: james.trosko@ht.msu.edu
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ISSN:0267-8357
1464-3804
DOI:10.1093/mutage/gei017