Correlations between Intercalator-induced DNA Strand Breaks and Sister Chromatid Exchanges, Mutations, and Cytotoxicity in Chinese Hamster Cells

Intercalator-induced DNA strand breaks in mammalian cells represent topoisomerase ll:DNA complexes trapped by intercalated. These complexes are detected as protein-associated DNA single-strand breaks (SSB) and DNA double-strand breaks (DSB) by filter elution. Using Chinese hamster lung fibroblasts (V79 cells) that were treated for 30 min with various concentrations of 4ˊ-(9-acridinylamino)methanesulfon-m-anisidide or 5-imino-daunorubicin, we measured DNA strand breaks (SSB and DSB), sister chromatid exchanges (SCE), mutations at the hypoxanthine:guanine phosphoribosyttransferase locus, and cell killing. Further, we correlated DNA strand breakage with the three other parameters. Both drugs induced SCE, mutations, and cell killing at concentrations which also produced reversible DNA strand breaks. While the quantity of DSB correlated with SCE, mutations, and cytotoxicity for both drugs, we found more SCE, mutations, and cytotoxicity per SSB in cells treated with 5-iminodaunorubicin than in those treated with 4ˊ-(9-acridinylam-ino)methanesulfon-m-anisidide. These data show that the DSB (but not the SSB) induced by 4ˊ-(9-acridinylamino)methane-sulfon-m-anisidide and 5-iminodaunorubicin at DNA topoisomerase II binding sites correlated closely with SCE, mutations, and cell killing and could therefore be responsible for their production.