The interaction between bleomycin and radiation on cell survival and DNA damage in mammalian cell cultures

Chinese hamster ovary (CHO) cells were exposed to various concentrations of bleomycin (BLM) for 0.5, 1, 2, 4, 6, or 24 hours, followed with graded doses (0 to 800 rad) or radiation. The response to this chemotherapy-radiation combination treatment was measured by cell survival studies and DNA damage as determined by alkaline elution assay. Isobolograms for 1 and 2 log cell kills showed that cytotoxicity from BLM and from radiation were additive at 4, 15 and 75 milliunit/ml (mu/ml) for 1 or 4 hour exposure. When the exposure time of BLM was extended to 24 hours, slightly supraadditivity of lethality was found for the combination treatment with pharmacologically pertinent concentrations of 4 or 15 mu/ml. Therefore 4, 15 and 75 mu/ml concentrations of BLM all interacted positively with all doses of radiation to give enhanced cell kill. The alkaline elution patterns from the BLM-radiation combination also showed an enhancing effect on single strand breaks of DNA from treated cells. A human oat cell carcinoma cell line (MEMAR cells) was also studied and found to be more sensitive to BLM than were CHO cells.