Carcinogenesis can be divided conceptually into four steps: tumor initiation, tumor promotion, malignant conversion, and tumor progression (Figure 17-1). The distinction between initiation and promotion was recognized through studies involving both viruses and chemical carcinogens.8,15 This distinction was formally defined in a murine skin carcinogenesis model in which mice were treated topically with a single dose of a polycyclic aromatic hydrocarbon (ie, initiator), followed by repeated topical doses of croton oil (ie, promoter),8 and this model has been expanded to a range of other rodent tissues, including bladder, colon, esophagus, liver, lung, mammary gland, stomach, and trachea.16 During the last 50 years, the sequence of events comprising chemical carcinogenesis has been systematically dissected and the paradigm increasingly refined, and both similarities and differences between rodent and human carcinogenesis have been identified.17,18 Carcinogenesis requires the malignant con...
