THE INTERACTION OF RADIATION AND INTERCALATING AGENTS IN NORMAL BONE MARROW CELLS AS EVALUATED BY SPLEEN COLONY ASSAY TECHNIQUE: THE EFFECTS OF BLEOMYCIN SULFATE AND ACT INOMYCIND.

The relationship between the way in which normal hemopoietic stem cells respond to irradiation alone or in the presence of bleomycin sulfate (BLM-S) and actinomycin 0 (ACT-D) was investigated. Single doses of BLM-S at 0.3 mg/kg and ACT-O at 0.10 mg/kg body weight were injected intravenously 1-6 hours prior to whole body irradiation and treatment was repeated twice more with time intervals. When assessed by survival of spleen colony forming units (CFU-S) of bone marrow cells (BMC), BLM-S alone caused only 10% reduction in survival compared to controls. There was not a significant difference in survival fraction (SF) when treatment with BLM-S was repeated twice more. On the other hand, ACT-O alone caused a 45% reduction in SF after the first injection and only a 10% reduction after the third injection. Increase in survival might be due to resistance induced in BMC after treatments with the drugs. The difference between the 'SF of BMC of mice exposed to doses of 1-3 Gy whole body irradiation was statistically significant with a p-value <0.05. When used in combination with radiation, neither BLM-S nor ACT-O caused a synergistic or additive effect. Although survival was seen to be lower for ACT-O treated animals, the effect was not as pronounced as expected. A significant change in the results was also not observed for fractionated doses of gamma rays in the presence of BLM-S and ACT-O injected at various time intervals. Results obtained from the administration of drugs at various time intervals before irradiation does not suggest a specific time for drug treatment prior to irradiation. These results also suggest that no potentiating effect is likely to be produced by a combination of BLM-S or ACT-O and radiation therapy in bone marrow cells. We therefore believe that these drugs induce a modest resistive response to the effects of radiation on bone marrow cells by a mechanism which is not yet understood. Therefore, using this agent repeatedly for cancer treatment might not cause severe adverse biological effects in bone marrow stem cells.