Modern criteria to determine the etiology of human carcinogens

Rapid identification of human carcinogens before their dissemination into society, and exposure of worker and lay populations is an important goal of cancer research. Retroactively, verification of in-place human carcinogens is also required to target their removal, and other preventive and therapeutic strategies. The hierarchy of methods used historically for evaluation of carcinogenic potential is epidemiology > animal bioassays > mechanistic studies, and the focus has been on single agents that are genotoxic. However, mechanistic research has revealed several obligatory steps in carcinogenesis, tumor promotion, and progression that can now be used in screening studies with human cells in vitro and animal bioassays. These approaches should be combined with molecular epidemiology and molecular pathology to identify human carcinogens with more emphasis on evaluating combinations of suspect agents and mechanisms of action of epigenetic carcinogens.