Induction of a mutation in an essential gene involved in cell growth
activation of oncogenes
inactivation of tumor suppressor genes, DNA repair genes, genes in
antioxidation response
Requires a fewrounds of cell division for the ‘fixation’ of the DNA damage
Fixation is not repair; Fixation = keep mutation in divided cells
DNA damage not enough to produce cancer
Non reversible
single treatment of genotoxic carcinogen --> induce mutation
Outcomes of initiated cells:
remain in a static nondividing state
acquire mutations incompatible with viability/ normal function; This cell will be removed by apoptosis
undergo cell division --> selectivegrowth and expansion of the
initiated cell population, through intrinsic or extrinsicfactors
Initiators
chemical carcinogens that function at the initiation stage
Highlyreactive electrophiles
Interact with nucleophiles in the cell (i.e., DNA, RNA, and protein)
Directlymutagenic
Once the injury to the DNA has occurred and is not repaired, the cell is permanently mutated
Some initiated cell following high dose exposure and/ or repeated dosing to genetoxic agents may be capable of progressing through all3 stages of carcinogeneis