The v-src oncogene may not be responsible for the increased radioresistance of hematopoietic progenitor cells expressing v-src

M. A. Santucci, P. Anklesaria, S. M. Anderson, I. J. Das, T. J. FitzGerald, H. Valinsky, K. R. Kase, M. A. Sakakeeny, J. S. Greenberger

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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 γ irradiation administered at the low- dose rate of 0.05 Gy/min, which is used clinically. The v-src-dependent nature of resistance to γ 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 γ irradiation. The D0 of parental 32D cl 3 cells kept at 39°C after γ 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 γ-radiation resistance of these cells at low dose rate.

Original languageEnglish (US)
Pages (from-to)297-303
Number of pages7
JournalRadiation research
Volume129
Issue number3
DOIs
StatePublished - Apr 29 1992

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ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Cite this

Santucci, M. A., Anklesaria, P., Anderson, S. M., Das, I. J., FitzGerald, T. J., Valinsky, H., Kase, K. R., Sakakeeny, M. A., & Greenberger, J. S. (1992). The v-src oncogene may not be responsible for the increased radioresistance of hematopoietic progenitor cells expressing v-src. Radiation research, 129(3), 297-303. https://doi.org/10.2307/3578029