This podcast with Dr. Sam Cohen and hosted by Dr. Peter Hall  concerns the publication of a STP committee chaired by Dr. Charles Wood concerning the role of increased cell proliferation in the evaluation of the mode of action of carcinogenesis, particularly for nongenotoxic chemicals.  Dr. Cohen emphasizes the importance of attention to details in assessing cell proliferation, with different approaches necessary for various tissues and circumstances.  He also emphasizes that the focus is on the number of cell replications, not necessarily the rate, and that it is the tissue stem cell population that is critical.  For nongenotoxic chemicals the mode of action always involves an increase in cell proliferation, and this can be utilized in designing a short (e.g. 90 days) study to screen for carcinogenesis in rodents.  Such a screen requires a labeling index (BrdU, Ki-67, PCNA) in addition to standard histopathology.  If positive, additional short term studies can be performed to evaluate the dose response in detail and to determine the mode of action and its relevance to humans.  Ultimately, this could replace the standard 2 year bioassay.

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