Alterations in oncogene expression and radiosensitivity in the most frequently used SV40-transformed human skin fibroblasts

Int J Radiat Biol. 1994 Jun;65(6):665-73. doi: 10.1080/09553009414550781.

Abstract

In comparison with primary cell cultures, SV40-transformed human skin fibroblasts, either from healthy donors or from patients suffering from ataxia-telangiectasia (AT) or xeroderma pigmentosum, are more resistant to the cytotoxic action of low LET 60cobalt gamma-rays as well as to high LET alpha-particles. Resistance factors calculated from D10's lie between 1.4 and 2.0. Northern blot analysis reveals spontaneous overexpression of the oncogenes c-myc, Ki-ras and c-raf and of the tumour suppressor gene p53 as a consequence of SV40 transformation. For c-myc, the increased expression is due to gene amplification and gene rearrangement. An even further increase in the expression of c-myc has been found for AT cells (AT5BI-VA) after moderate doses of 60cobalt gamma-irradiation. A possible correlation between SV40-induced changes in gene expression and cellular radioresistance is discussed.

MeSH terms

  • Alpha Particles
  • Americium
  • Cell Transformation, Viral / genetics*
  • Cobalt Radioisotopes
  • Energy Transfer
  • Gamma Rays
  • Gene Amplification
  • Gene Expression Regulation, Viral / radiation effects*
  • Genes, myc
  • Genes, p53
  • Genes, ras
  • Humans
  • Oncogenes*
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-raf
  • Simian virus 40 / genetics*
  • Skin

Substances

  • Cobalt Radioisotopes
  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Americium