Etoposide exerts its cytotoxic effect in cancer chemotherapy through which mechanism?

• A Formation of a cleavable complex with topoisomerase II, causing DNA strand breaks ✓
• B Inhibition of topoisomerase I, preventing DNA religation
• C Alkylation of DNA at the N7 position of guanine
• D Generation of free radicals leading to DNA strand scission

Explanation

Etoposide stabilizes the covalent topoisomerase II-DNA cleavable complex, preventing rejoining of broken strands and producing double-strand breaks that trigger cell death in late S and G2 phases. Topoisomerase I poisoning is the mechanism of camptothecins such as irinotecan and topotecan. Guanine N7 alkylation defines nitrogen mustard-type alkylators, and free radical generation is typical of anthracyclines and bleomycin, eliminating those options.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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