Chromosome damage induced by DNA topoisomerase II inhibitors combined with γ-radiation in vitro

Combined radiation and antineoplastic drug treatment have important applications in cancer therapy. In the present work, an evaluation was made of two known topoisomerase II inhibitors, doxorubicin (DXR) and mitoxantrone (MXN), with gamma-radiation. The effects of DXR or MXN on gamma-radiation-induced chromosome aberrations in Chinese hamster ovary (CHO) cells were analyzed. Two concentrations of each drug, 0.5 and 1.0 mu g/ml DXR, and 0.02 and 0.04 mu g/ml MXN, were applied in combination with two doses of gamma-radiation (20 and 40 cGy). A significant potentiating effect on chromosomal aberrations was observed in CHO cells exposed to 1.0 mu g/ml DXR plus 40 cGy. In the other tests, the combination of gamma-radiation with DXR or MXN gave approximately additive effects. Reduced mitotic indices reflected higher toxicity of the drugs when combined with radiation.