II. Intercalating agents: ANTHRACYCLINE ANTIBIOTICS
Mechanism
- primary mechanism: intercalation in major groove of DNA
causing several cytotoxic actions:
- inhibition of topoisomerase II
- single- and double-strand breaks (mutagenic) or sister chromatid exchange (carcinogenic)
secondary mechanisms:
- interact with cell membranes to alter fluidity and ion transport
- in the presence of NADPH, they react with cytochrome P450 reductase to form superoxide anion radicals à may also cause unique cardiotoxicity
- CELL CYCLE NON-SPECIFIC (CCNS), but maximal toxicity in S phase (at low concentrations will pass through S and die in G2)