Drug-Induced Cytotoxicity in Tissue Culture

Topoisomerase II is a requisite enzyme that cleaves both strands of double-stranded DNA, allowing for passage of a second DNA duplex, resulting in the unwinding of chromosomal DNA. Topo II is covalently bound to the 5′-end of the cleaved DNA in a reversible reaction. However, treatment with numerous chemotherapeutic agents, including the epipodophyllotoxins, amsacrine and Adriamycin, stabilize the topo II-DNA complex with the DNA in the cleaved state (reviewed 1 ,2 ). The mechanisms by which complex stabilization and DNA strand breaks lead to cell death have not been elucidated, but in general, the magnitude of drug-induced DNA strand-break production correlates with the magnitude of drug-induced cytotoxicity (3 ,4 ). However, there are exceptions to this general rule (5 ).