title: The v-src oncogene may not be responsible for the increased radioresistance of hematopoietic progenitor cells expressing v-src.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: M A
authors.initials: MA
authors.lastname: Santucci
authors.forename: P
authors.initials: P
authors.lastname: Anklesaria
authors.forename: S M
authors.initials: SM
authors.lastname: Anderson
authors.forename: I J
authors.initials: IJ
authors.lastname: Das
authors.forename: T J
authors.initials: TJ
authors.lastname: FitzGerald
authors.forename: H
authors.initials: H
authors.lastname: Valinsky
authors.forename: K R
authors.initials: KR
authors.lastname: Kase
authors.forename: M A
authors.initials: MA
authors.lastname: Sakakeeny
authors.forename: J S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: 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
chemical_list: D007377:Interleukin-3