Cell proliferation: concluding remarks

In beginning this overview, I want to acknowledge the fact that, even though I disagree with most of his conclusions, Bruce Ames has played an important role in further stimulating interest in cell proliferation in carcinogenesis. This meeting has provided a balanced discussion of the current state of knowledge in this field. It has also highlighted the complexities of cell proliferation, the need for further mechanistic studies, and the desirability of developing new methods that can be used to precisely quantitate the various parameters related to cell proliferation in the intact organism. At this meeting and in a recent paper (1), Ames has put forth several postulates that I believe represent an oversimplification of the multistage carcinogenic process. These postulates include the following: a) the aging process per se is a major factor in human cancer causation; b) oxidative damage due to endogenous factors plays a major role in human cancer causation; c) mitogenesis (induced cell division) plays a major role in carcinogenesis by increasing mutagenesis; d) the standard National Toxicology Program (NTP) rodent bioassay frequently yields unreliable results with respect to predicting human carcinogens; and e) synthetic pesticides and certain other synthetic chemicals pose lesser carcinogenic risks than nature's pesticides and other naturally occurring chemicals in various food stuffs. Elsewhere, I have reviewed evidence that calls into question these conclusions (2,3). Some of this evidence was discussed at this meeting and will be briefly reviewed here. Some of Ames' postulates may apply in specific cases. I do not believe, however, that there is sufficient evidence at the present time to use these postulates as a general basis for discarding current methods of carcinogen detection and risk extrapolation or for altering current guidelines for regulating potential carcinogens. With respect to Ames' criticism of the standard NTP rodent carcinogen bioassay, we have heard evidence