Stem cell theory of carcinogenesis.

Our present understanding of the carcinogenic process, involving complex interactions of genetic, developmental, sex, dietary and environmental factors during the multistage initiation/promotion/progression process of carcinogenesis, would lead us to reject simplistic non-biologically based risk assessment models. This understanding, plus recent results of the National Toxicology Bioassay program and of the studies of short-term tests for genotoxicity, has challenged the primary paradigm of 'carcinogens as mutagens' which governs our current risk assessment models. The concepts of the stem cell theory of cancer, of oncogenes/tumor suppressor genes, of gap junctional intercellular communication, and of mutagenic and epigenetic mechanisms must be integrated into a biologically-based model of the multistage nature of carcinogenesis. Current understanding of the complex interactions during this process prevents us from believing that a simple and accurate, biologically-based risk assessment model will be developed soon, if ever.