Journal
INTERNATIONAL JOURNAL OF TOXICOLOGY
Volume 29, Issue 4, Pages 344-357Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1091581810371384
Keywords
epigenetic toxicology; adult stem cells; Barker hypothesis; gap junctional intercellular communication; chemical toxicity
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Funding
- NIEHS NIH HHS [R01 ES013268-01A2] Funding Source: Medline
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Chemicals are known to be associated with birth defects, cancer, cardiovascular diseases, immunological, reproductive, and neurological disorders. In response to recent reviews of limitations of current concepts and techniques for toxicity testing, this commentary challenges the paradigm that chemicals are directly responsible for DNA damage in the genomic-nuclear DNA in relevant cells of the human body. This challenge is not that mutations do not play roles in human-inherited or somatic diseases but that chemical exposures bring about disease end points by epigenetic mechanisms or by alterations in adult stem cell numbers in utero (ie, the Barker hypothesis) or postnatally, by selecting preexisting mutated cells. Classic concepts, that is, multi-stage, multimechanism process of carcinogenesis, stem cell theory of cancer, and newer and ignored concepts, such as cancer stem cells and cell-cell communication, will be used to support the view that the toxic effect of chemicals is mediated by nonmutagenic mechanisms at human relevant exposures.
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