Differential radiosensitising effect of the scid mutation among tissues, studied using high and low dose rates: implications for prognostic indicators in radiotherapy.

Abstract

To assess whether radiation-sensitive or radiation-resistant individuals should in principle be predicted equally well using different cell types, the effect of the scid mutation on the radiosensitivity of colony-forming cells in different murine tissues was assessed using high and low dose-rates. At high dose-rate, the amount of radiosensitization due to the scid mutation was greater in epithelial cells of the intestine and the kidney than in haemopoietic and fibroblastoid cells in the bone marrow, when expressed as a dose reduction factor. However, this greater radiosensitization in intestine and kidney did not translate into bigger differences in SF2 (surviving fraction at 2 Gy) or SF3.5. This was because of the greater inherent radioresistance of the epithelial cells compared with the marrow cells, resulting in smaller changes in cell survival from a given dose. Reductions in cell survival due to the mutation increased with increasing dose as expected at high dose rate. The changes in SF2 and SF3.5 due to the scid mutation were not significantly increased by using low dose-rates, because of the tendency for the presence of some low dose-rate sparing in the scid cells as well as the marked amount observed in the wild-type cells. The implications for predictive testing in radiotherapy are that for genetic defects resulting in the same type of radiosensitization phenomenon shown here for scid cells, radiosensitive or radioresistant cell types may still give similar differentials in response due to the mutation when SF2 is used as an endpoint.(ABSTRACT TRUNCATED AT 250 WORDS)