Induction of cytogenetic adaptive response of mouse bone marrow cells to radiation by therapeutic doses of bleomycin sulfate and actinomycin D as assayed by the micronucleus test.

An in vivo micronucleus assay using bone marrow cells of Syrian albino male mice for identifying the possibility of induction of adaptive response to various doses of radiation following treatment with chemotherapeutics is described. Single doses of bleomycin sulfate (BLM-S) at 300 micrograms/kg and actinomycin-D (ACT-D) at 10 micrograms/kg body weight (therapeutic dose range) were injected intravenously 3 h prior to whole body gamma-irradiation. Irradiation at various doses from 1-4 Gy was carried out at a dose rate of 45 cGy/min. Animals were killed at 24, 36 and 48 h post-irradiation. The results obtained in this study clearly indicate a significant difference for radiation induced micronuclei (MN) in polychromatic erythrocytes (PCEs) with P value < 0.001 over the dose range used. When used in combination with radiation, neither ACT-D nor BLM-S caused a synergistic or additive effect. Irradiated animals showed a higher incidence of micronuclei formation in the presence of ACT-D and BLM-S. However, in both cases, the number of MN induced in PCEs was less than the sum of MN induced by radiation and ACT-D or BLM-S alone. The effect of combined treatment was reduced by a factor of 1.5 for BLM-S and greater than 1.5 for ACT-D treated animals. These observations indicate that although a small amount of ACT-D or BLM-S reaches the bone marrow cells via the circulation, these drugs might produce effects which make bone marrow cells resistant to the clastogenic effects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe adverse biological effects in normal hemopoeitic tissue.