Dose-rate effects of gamma-ray-induced mutations in cultured mammalian cells

The dose-rate dependency of three radiobiological parameters, cell killing and mutations resistant to 6-thioguanine (6-TGr) and to methotrexate (MTXr), were studied in populations of mouse L5178Y cells exposed to gamma-rays. When the dose rate was reduced from 50 rad/min to 0.8 rad/min, the shape of the dose--response curves changed from sigmoidal to exponential for cell killing, from upward concave to linear in 6-TGr mutations and remained linear in MTXr mutations. A linear quadratic model appears capable of explaining the cell killing and 6-TGr mutations but not the MTXr mutations. The declining patterns of induced mutation frequencies of 6-TGr and MTXr with decreasing dose rate seem to be similar. The addition of DMSO resulted in protection of cells from cell killing, 6-TGr and MTXr mutations with acute exposure, but had little effect with chronic exposure. The reduction of mutation frequency of the 6-TGr marker with chronic exposure was eliminated by holding cells in ice-cold condition during irradiation. These results suggest that there may be two components of induced mutation. One results primarily from repairable damage induced by the indirect action of radiation and shows a clear dose-rate dependency. The other is mainly from no-repairable damage by the direct action of radiation and is only slightly dose rate-dependent. Under chronic exposure conditions, the latter may predominate.