The discovery that transforming genes of oncogenic retroviruses are transduced variants of eucaryotic genes launched the current era of molecular carcinogenesis. The interpretation of that discovery and the molecular insights that followed, however, depended on the foundation established by four prior decades of carcinogenesis research. Studies in animals had established that certain chemicals could cause malignant tumors, that cancer induction is a multistage process, and that carcinogenesis is organ specific in humans and other mammals (Yuspa and Poirier, 1988). Subsequent studies in cell culture proved that neoplastic transformation by chemicals is inductive rather than selective, and that somatic mutations are an important component of cancer pathogenesis. Cellular enzymes were identified that activated or detoxified chemical carcinogens, and DNA was recognized as the critical target for activated carcinogens (Miller, 1978). The development of methods to evaluate carcinogenesis in cultured human cells provided the foundation for studies of comparative carcinogenesis at the molecular level (Yuspa and Poirier, 1988; Harris, 1991). While recent genetic analyses have defined intimate details of the cellular pathways that are altered in response to carcinogenic stimuli and revealed the structural basis for many of these alterations, they must be evaluated in the context of cancer's multiple stages: initiation, promotion, and malignant conversion (Yuspa and Poirier, 1988; Harris, 1991).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)