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 gamma irradiation administered at the low-dose rate of 0.05 Gy/min, which is used clinically. The v-src-dependent nature of resistance to gamma 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 degrees C. Cells transformed by v-src and grown at either 34 or 39 degrees 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 gamma irradiation. The D0 of parental 32D cl 3 cells kept at 39 degrees C after gamma irradiation was reduced significantly compared to the D0 of these cells kept at 34 degrees 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 degrees 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 gamma-radiation resistance of these cells at low dose rate.
Santucci
M A
MA
Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester 01655.
Anklesaria
P
P
Anderson
S M
SM
Das
I J
IJ
FitzGerald
T J
TJ
Valinsky
H
H
Kase
K R
KR
Sakakeeny
M A
MA
Greenberger
J S
JS
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D006358:Hot Temperature; D007377:Interleukin-3 / Q000502:physiology; D051379:Mice; D009154:Mutation; D009857:Oncogenes / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D012192:Retroviridae Infections
D007377:Interleukin-3