Chromosomal aberrations induced in mice bone marrow by treating with cisplatin and irradiation

Background: The aim of this study was to quantify the combined effect of cisplatin and radiation on chromosomal damage with emphasis on the time interval between cisplatin and radiation. Methods and Materials: Bone marrow of female NMRI-nu(+) mice was taken as a model system for a highly proliferative tissue AR irradiated with cobalt-60 (1 to 4 Gy). Cisplatin was injected intraperitoneally (ip) at 1.1 to 36 mg/kg. Cisplatin was given at various time intervals before and after radiation. Bone marrow and metaphases were prepared according to standard procedures. Results: The percentage of aberrant metaphases after radiation or cisplatin alone increased in a dose- dependent manner (sigmoidal dose-response curve). Combining both modalities led to additive values at all time points for the percentage of aberrant metaphases. Borderline significant (p < 0.05) supraadditive effects were found 2 hours before or 1 hour after irradiation. However, a supraadditive percentage of aberrant chromosomes was found only at 2 or 1.5 hours with cisplatin before irradiation indicating the dependence of supraadditivity on the chosen parameter. Conclusion: It is doubtful to expect a true supraadditive or 'radiosensitizing' effect, e. g. in the clinical setting from combined treatment with cisplatin and radiation. Rather, cisplatin might act as an independent cytotoxic agent.