The influence of two radiosensitizers on the induction of chromosome aberrations in human lymphocytes by X-radiation

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Abstract
The influence of metronidazole and misonidazole on the induction of unstable chromosome aberrations in human lymphocytes was examined. A suitable treatment concentration of 8 mM was chosen for both chemicals because this produced a maximal effect when combined with 3.0 Gy [Gray] X rays without adversely affecting cell viability. Misonidazole concentrations above 20 mM resulted in a severely reduced yield of metaphase spreads after 48 h in culture. Under conditions of anoxia, the addition of 8 mM sensitizer without irradiation produced no increase in the number of gross chromosome aberrations. A small, statistically non-significant increase in aberration yields was observed in treated lymphocytes irradiated at venous O2 concentration. Radiation dose-response curves for anoxic blood containing 8 mM metronidazole or misonidazole were compared with previously obtained curves for dicentric and total aberration induction in untreated anoxic blood. Values calculated from these curves for the enhancement ratios at doses above about 1.0 Gy were 1.4 and 2.2 for metronidazole and misonidazole, respectively. These values are comparable with enhancement ratios observed in other biological systems.