Effect of doxorubicin on cell survival and micronuclei formation in HeLa cells exposed to different doses of gamma-radiation

Purpose: The present study was undertaken to obtain an insight into the combined effects of doxorubicin with radiation on the cell survival and micronuclei induction in HeLa cells. Material and Methods: HeLa S3 cells were allowed to grow till they reached plateau phase, inoculated with 10 μg/ml doxorubicin hydrochloride and then exposed to 0, 0.5, 1, 2 and 3 Gy γ-radiation. Clonogenicity of cells was measured using the colony forming assay, micronuclei formation using the micronucleus assay. Results: The treatment of HeLa cells with doxorubicin (adriamycin) for 2 hours before exposure to different doses of γ-radiation resulted in a significant and dose-dependent decline in the cell survival and cell proliferation when compared to the PBS + irradiation group. Conversely, the frequency of micronuclei increased in a dose-related manner in both the PBS + irradiation and doxorubicin + irradiation groups. The pretreatment of HeLa cells with doxorubicin before irradiation to various doses of γ-rays resulted in a significant elevation in the frequency of micronuclei when compared with the concurrent PBS + irradiation group. The dose-response relationship for both PBS + irradiation and doxorubicin + irradiation groups was linear. The correlation between cell survival and micronuclei induction was also determined for PBS or doxorubicin + irradiation group, where the clonogenicity of cells declined with the increase in micronuclei formation. The correlation between cell survival and micronuclei induction was linear quadratic for both PBS + irradiation and doxorubicin + irradiation groups. Conclusion: From our study it can be concluded that combination treatment with doxorubicin and radiation increased the genotoxic effect of the either treatment given alone.