Alterations in oncogene expression and radiosensitivity in the most frequently used SV40-transformed human skin fibroblasts.
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.
Lücke-Huhle
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Kernforschungszentrum Karlsruhe, Institut für Genetik, Germany.
D000512:Alpha Particles; D000576:Americium; D002472:Cell Transformation, Viral / Q000235:genetics*; D003037:Cobalt Radioisotopes; D004735:Energy Transfer; D005720:Gamma Rays; D005784:Gene Amplification; D015967:Gene Expression Regulation, Viral / Q000528:radiation effects*; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D009857:Oncogenes; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf; D013539:Simian virus 40 / Q000235:genetics*; D012867:Skin
D003037:Cobalt Radioisotopes; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D000576:Americium