Journal
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Volume 616, Issue 1-2, Pages 7-10Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrfmmm.2006.11.002
Keywords
dose-response characteristics; metastatic tumor; histones; methylation; chromatin remodeling
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The U. S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment encourages the use of mechanistic data in the assessment of human cancer risk at low (environmental) exposure levels. The key events that define a particular mode of action for tumor formation have been concentrated to date more on mutational responses that are broadly the result of induced DNA damage and enhanced cell proliferation. While it is clear that these processes are important in terms of tumor induction, other modes that fall under the umbrella of epigenetic responses are increasingly being considered to play an important role in susceptibility to tumor induction by environmental chemicals and as significant modifiers of tumor responses. Alterations in gene expression, DNA repair, cell cycle control, genome stability and genome reprogramming could be the result of modification of DNA methylafion and chromatin remodeling patterns as a consequence of exposure to environmental chemicals. These concepts are described and discussed. Published by Elsevier B.V.
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