DNA damage and cytotoxicity of mitoxantrone and doxorubicin in doxorubicin-sensitive and -resistant human colon carcinoma cells

The effects of mitoxantrone (Mx) and doxorubicin (Dx) on cytotoxicity and DNA damage as assayed by alkaline elution were studied in two human colon adenocarcinoma cell lines sensitive (LoVo) and resistant (LoVo/Dx) to doxorubicin. Mx was more cytotoxic than Dx to LoVo cells and was partially cross-resistant in LoVo/Dx. In LoVo cells, Mx produced about 5 times more DNA single-strand breaks (DNA-SSB) than Dx, but both drugs caused an equal number of DNA double-strand breaks (DNA-DSB). In LoVo/Dx cells, the number of DNA-DSB was very low for both Dx and Mx, but DNA-SSB were about 20 times higher for Mx. In LoVo cells, the number of DNA-DSB and protein-associated SSB were similar at equitoxic concentrations. For LoVo/Dx, the partial cross-resistance of Mx might be explained by the much higher number of DNA-SSB produced by this drug.