In the classic two-stage model of chemical carcinogenesis, which statement correctly distinguishes initiation from promotion?

• A Initiation is reversible and causes DNA damage, while promotion is irreversible and stimulates cell proliferation
• B Both initiation and promotion are irreversible, but only initiation requires a genotoxic agent
• C Initiation involves irreversible DNA mutation, while promotion is reversible and stimulates proliferation of initiated cells ✓
• D Promotion causes the initial DNA mutation, while initiation provides the selective growth advantage

Explanation

Initiation involves irreversible DNA damage caused by a genotoxic agent. Promotion involves reversible stimulation of cell proliferation of the initiated clone by agents that are not themselves mutagenic. The key distinction is that initiation is irreversible while promotion requires continued exposure to the promoter and is reversible if the promoter is withdrawn. This is the classic Berenblum model of skin carcinogenesis.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

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