CHROMOSOME-DAMAGE INDUCED BY DNA TOPOISOMERASE-II INHIBITORS COMBINEDWITH GAMMA-RADIATION IN-VITRO

Combined radiation and antineoplastic drug treatment have important ap plications in cancer therapy. In the present work, an evaluation was m ade of two known topoisomerase II inhibitors, doxorubicin (DXR) and mi toxantrone (MXN), with gamma-radiation. The effects of DXR or MXN on g amma-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 combina tion with two doses of gamma-radiation (20 and 40 cGy). A significant potentiating effect on chromosomal aberrations was observed in CHO cel ls exposed to 1.0 mu g/ml DXR plus 40 cGy. In the other tests, the com bination of gamma-radiation with DXR or MXN gave approximately additiv e effects. Reduced mitotic indices reflected higher toxicity of the dr ugs when combined with radiation.