Mechanisms of Rodent Liver Carcinogenesis

Stimulation of DNA synthesis by peroxisonte proliferators, including DEHP, should be viewed differently from the stimulation of DNA synthesis by xenobiotic chemicals which stimulate restorative hyperplasia after hepatic necrosis induced by the toxicity of the chemical. The emerging picture of the control mechanisms for hepatocyte proliferation suggests that rather few and distinct factors are involved. The stimulation of DNA synthesis by peroxisome proliferators should be examined in the context of the effects of these factors. Comparisons with other xenobiotics show that induction of DNA synthesis at rates comparable to those of peroxisome proliferators is not sufficient to explain the rates of carcinogenicity associated with peroxisonie proliferators. These considerations lead to the conclusion that although DNA synthesis enhances the incidence of neoplasia, it should not be viewed as a complete carcinogen, nor should it be considered as resulting in initiation at rates that can explain the carcinogenic potency of compounds such as peroxisome proliferators.

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