The effects of oxygen and hypoxic cell sensitizers on chromosome aberration induction in human lymphocytes

Normal human blood was exposed at 370C to 250 kVp X-rays under conditions of anoxia and of equilibration with oxygen. The numbers of observed dicentric aberrations were fitted to the expression Y = αD + βD2 and from these curves an OER estimate of 2.8 at 5.0 Gy was obtained. The dicentric yield was also measured after blood held at various oxygen tensions was exposed to 3.0 Gy or 0.75 Gy X-rays. No difference was observed between the values at the lowest oxygen concentration of less than 2 ppm and at 250 ppm. Above 250 ppm there was a steep rise in the number of dicentrics observed but at oxygen levels above 1% the dicentric yield was again much less dependent on the oxygen concentration. The experiments were repeated using different concentrations of 'Flagyl' and Ro 07 0582 which both showed a maximum effect at 4 to 8 mM. Dose response data obtained in the presence of 8 mM sensitizer were again fitted to the quadratic expression and enhancement ratios of 2.2 and 1.4 estimated for Ro 07 0582 and 'Flagyl' respectively. Blood irradiated at venous oxygen tension in the presence of each of these chemicals showed an unchanged dicentric yield in the case of 'Flagyl' and a slight increase with Ro 07 0582 at a dose of 1.0 Gy. (Auth.)