Alterations in Oncogene Expression and Radiosensitivity in the Most Frequently Used SV40-transformed Human Skin Fibroblasts

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 γ-rays as well as to high LET α-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 γ-irradiation. A possible correlation between SV40-induced changes in gene expression and cellular radioresistance is discussed.