INDUCTION OF CYTOGENETIC ADAPTIVE RESPONSE OF MOUSE BONE-MARROW CELLSTO 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 re sponse to various doses of radiation following treatment with chemothe rapeutics is described. Single doses of bleomycin sulfate (BLM-S) at 3 00 mu g/kg and actinomycin-D (ACT-D) at 10 mu g/kg body weight (therap eutic dose range) were injected intravenously 3 h prior to whole body gamma-irradiation. Irradiation at various doses from 1-4 Gy was carrie d 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 indi cate a significant difference for radiation induced micronuclei (MN) i n polychromatic erythrocytes (PCEs) with P value < 0.001 over the dose range used. When used in combination with radiation, neither ACT-D no r BLM-S caused a synergistic or additive effect. Irradiated animals sh owed a higher incidence of micronuclei formation in the presence of AC T-D and BLM-S. However, in both cases, the number of MN induced in PCE s 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 obser vations indicate that although a small amount of ACT-D or BLM-S reache s the bone marrow cells via the circulation, these drugs might produce effects which make bone marrow cells resistant to the clastogenic eff ects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe advers e biological effects in normal hemopoeitic tissue.