Mechanisms of unusually high antioxidant activity of RSV-SR-transformed cells and of its suppression by activated p21^ras

We have previously demonstrated that hamster embryo fibroblasts (HEFs) transformed by Rous Sarcoma virus, Schmidt-Ruppin strain (RSV-SR) are highly resistant to damage by H₂O₂ (H₂O₂^R), (in contrast to HEFs transformed spontaneously, or by bovine adenovirus and SV40), while N-ras transfectaon of RSV-SR transformants leads to suppression of pp60^v-src= and of H₂O₂. In this study we have examined (I) mechanisms of antioxidant activity (AOA) of HEFs transformed by these agents and (2) the possible role of the v-src gene in unusually high AOA of RSV-SR transformants and of activated ras oncogenes in its suppression. All transformants exhibit increased catalase and glutathione peroxidase (GP) activities, while SOD, glutathione and glutathione reductase (GR) were reduced. As compared with other transformants, the significantly higher catalase and the low SOD activities were characteristic of RSV-SR-transformants, while an increase in GP was observed in all types of transformants. Correspondingly, RSV-SR-transformants showed an extremely high H₂O₂-catabolizing activity (H₂O₂^CA) and no lipid peroxidation chain reaction (LPCR). N-ras-induced suppression of pp60^v-src of RSV-SR-transformed HEFs coincided with the suppression of catalase, GP, H₂O₂^R and H₂O₂^CA. However, suppression of catalase and GP was also observed in N-ras- and Ha-ras-transfected, spontaneously transformed HEFs. Thus, extremely high catalase activity and suppression of LPCR are apparently the main mechanisms of the unusually high H₂O₂ of RSV-SR transformants, while its suppression by activated ras oncogenes may also take place in some transformants, free of v-src activity.