Radiosensitizing effects of gemcitabine on aerobic and chronically hypoxic HeLa and MRC5 cells in-vitro

Gemcitabine (2′, 2′-difluoro-2′- deoxycytidine, an analogue of deoxycytidine) is a relatively new drug with wide range of anti-cancer activity. In this study, radiosensitizing effects of gemcitabine was investigated on HeLa and MRC5 human originated cell lines under both chronically hypoxic and normoxic conditions using the micronucleus (MN) assay. For induction of chronic hypoxia, the cell culture flasks were saturated with N2 gas. To evaluate the radiosensitizing effects, in the presence of the non-genotoxic concentration (1ng/ml) of gemcitabine, cells were exposed to different doses (0.5, 1, 2 Gy) of X-ray in both chronically hypoxic and normoxic conditions. Results showed that there was no significant difference in MN induction under chronically hypoxic and normoxic condition when using 1 ng/ml gemcitabine alone, however in the absence of drug, MN induction was significantly different in irradiated cells (P<0.01). Radiosensitizing effects of gemcitabine in chronic hypoxic condition was greater than normoxic condition in both cell lines (P<0.01), although more pronounced in HeLa cells. Radiosensitizing effects and greater dose modifying factor of gemcitabine under depleted oxygen condition is not clearly understood. It might be due to depletion of deoxynocleotides pools via inhibition of ribonucleotide reductase and mismatched nucleosides incorporation into DNA after radiation exposure.