Cell proliferation and carcinogenesis: a brief history and current view based on an IARC workshop report. International Agency for Research on Cancer.

The International Agency for Research on Cancer recently convened a Working Group of Experts (June 11-18, 1991) to discuss the use of information on carcinogenesis mechanisms in carcinogenic risk identification. The role of cell proliferation in carcinogenesis was among the items discussed in detail. It was recognized that cell proliferation is an important mechanistic aspect for both genotoxic and nongenotoxic carcinogens. It may act at each stage of the carcinogenesis process, altering the size of the pool of cells at risk for a next event. Cell proliferation was considered to be important, especially as a) an integral part of the process of converting DNA adducts to mutation, b) an enhancing factor for the mutation frequency by inducing errors in replication, and c) an important factor in determining dose-response relationships for some carcinogens. It was also recognized that not all agents that induce cell proliferation are necessarily involved in carcinogenesis; for example, a) not all skin hyperplasia-inducing compounds are skin tumor promoters, b) agents that induce "regenerative" cell proliferation appear to have different effects on tumor induction from agents that have a direct mitogenic effect, and c) the carcinogenic activity of many nonmutagenic agents depends on the continuous administration of the agent. In addition, tissues with a high rate of cell proliferation do not have a higher risk of developing cancer. Thus, no simple relationship exists between cell proliferation and carcinogenesis.