The Combination Cyclophosphamide with Radiation Increases Tumour Cure in Ehrlich Ascites Carcinoma Bearing Mice as well as DNA Damage in the Normal Mice Bone Marrow Exposed to Different Doses of Γ-Radiation

Abstract

Alterations in the radiation-induced micronuclei formation was studied in mice bone marrow treated with 0.5mg/kg body weight (1/500th of the LD50) of cyclophosphamide (CPA) before exposure to 0, 0.5, 1, 2 and 3Gy of γ-radiation. Irradiation of animals caused a dose dependent elevation in the Micro-nucleated Polychromatic Erythrocytes (MPCE) and Micro nucleated Norm chromatic Erythrocytes (MNCE) in the bone marrow of mice at 24h post-irradiation. Treatment of mice with 0.5mg/kg CPA elevated the radiation-induced MPCE significantly up to 2Gy irradiation and showed a significant decline thereafter when compared to the concurrent sterile physiological saline (SPS) treated irradiated group. The frequency of radiation-induced MNCE also showed a significant elevation after CPA treatment at all exposure doses. In a separate experiment the effect of 0.5mg/kg b. wt. CPA was evaluated in combination with radiation in the Ehrlich Ascites Carcinoma bearing mice (EAC). The combination of 0.5mg/kg b. wt. of CPA with 1, 2, 4, 6 and 8Gy of irradiation increased both the Median Survival Time (MST) and Average Survival Time (AST) of the EAC bearing mice when compared with the SPS+ irradiation and the maximum effect was observed in mice that received CPA and 8Gy of radiation. Our study demonstrates that the risk of genomic instability and mutagenesis outweighs the benefit accrued in the tumor bearing mice receiving combination of CPA and ionizing radiation.