Cards (6)

    • 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 few rounds 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 --> selective growth and expansion of the
    initiated cell population, through intrinsic or extrinsic factors
  • Initiators
    • chemical carcinogens that function at the initiation stage
    • Highly reactive electrophiles
    • Interact with nucleophiles in the cell (i.e., DNA, RNA, and protein)
    • Directly mutagenic
    • 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 all 3 stages of carcinogeneis
    • these agents are called Complete Carcinogens