Repair processes and radiation quality in neoplastic transformation of mammalian cells

Appropriate in vitro mammalian cell systems facilitate the study of cellular mechanisms of radiation oncogenesis. C3H 10T1/2 cells derived from mouse embryo have been used to study the effects of protracted irradiation on cell killing and incidence of neoplastic transformation. Neoplastic transformation in these cells results in the appearance of colonies of densely piled up, disorganized cells that grow on top of the contact inhibited monolayer of nontransformed cells. Protracted exposures of 60Co gamma rays or fission-spectrum neutrons (from the JANUS reactor at the Argonne National Laboratory) were given either at low dose rates or as multifractionated regimens using high dose rates. Dose protraction of gamma rays by multifractionation at a high dose rate (50 rad/min) results in appreciable reduction in cell killing and also significantly reduces the incidence of neoplastic transformation. Irradiation at a low dose rate has the same qualitative effect. In contrast, protracted exposures of fission-spectrum neutrons, given at a low dose rate (0.086 or 0.43 rad/min), result in significant enhancement of the frequency of transformation in the dose region of up to 80 rad. However, the survival of cells is essentially the same as that for the same single dose of neutrons given at a high dose rate. These observations are consistent with net "error-free" repair of transformational damage following protracted exposure of a low LET radiation and possibly a net "error-prone" repair of transformational damage after protracted irradiations with fission-spectrum neutrons.