Multi-stage Theory of Chemical Carcinogenesis Initiation --------Genetic events Chemical Carcinogens(Direct and Indirect Carcinogens) Promotion Epigenetic events Tumor promoters Murine skin carcinogenesis model A single dose of polycyclic aromatic hydrocarbon(PAH, Initiator) Repeated doses of croton oil(promoter) Malignant conversion Progression -----Genetic and epigenetic events10 Multi-stage Theory of Chemical Carcinogenesis Initiation -----------Genetic events Chemical Carcinogens (Direct and Indirect Carcinogens) Promotion -------Epigenetic events Tumor promoters – Murine skin carcinogenesis model: • A single dose of polycyclic aromatic hydrocarbon (PAH, initiator) • Repeated doses of croton oil (promoter) Malignant conversion Progression ------Genetic and epigenetic events