The v-src Oncogene May Not Be Responsible for the Increased Radioresistance of Hematopoietic Progenitor Cells Expressing v-src

Infection of the IL-3-dependent, myeloid progenitor cell line 32D cl 3 with murine retroviruses that contain either the wild-type or a temperature-sensitive mutant v-src can render these cells growth-factor independent. These cells also became resistant to ? irradiation administered at the low-dose rate of 0.05 Gy/min, which is used clinically. The v-src-dependent nature of resistance to ? irradiation was examined by studying four clones of 32D cl 3 cells that had been infected with a retrovirus carrying the tsLA31A mutant of v-src. The tyrosine-specific kinase activity of this mutant is dramatically reduced at the nonpermissive temperature of 39°C. Cells transformed by v-src and grown at either 34 or 39°C, in the presence or absence of IL-3, demonstrated a significantly higher D₀ compared to parental cells examined under identical conditions. In addition, expression of v-src abrogated the synergistic killing effect of heat and ? irradiation. The D₀ of parental 32D cl 3 cells kept at 39°C after ? irradiation was reduced significantly compared to the D₀ of these cells kept at 34°C. This contrasts with data from 32D cl 3 cells infected with either the wild-type v-src or the temperature-sensitive mutant, neither exhibited a synergistic effect in the D₀ at either 34 or 39°C. Therefore, while continuous expression of a v-src gene product is required for maintenance of the growth-factor-independent state, v-src does not appear to be responsible for the increased ?-radiation resistance of these cells at low dose rate.