title: Mechanisms of unusually high antioxidant activity of RSV-SR-transformed cells and of its suppression by activated p21ras.
abstract: 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 H202 (H2O2R), (in contrast to HEFs transformed spontaneously, or by bovine adenovirus and SV40), while N-ras transfection of RSV-SR transformants leads to suppression of pp6Ov-scr and of H2O2R. In this study we have examined (1) 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 H202-catabolizing activity (H2O2CA) and no lipid peroxidation chain reaction (LPCR). N-ras-induced suppression of pp60v-scr of RSV-SR-transformed HEFs coincided with the suppression of catalase, GP, H202 and H202CA. 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 H202R of RSV-SR transformants, while its suppression by activated ras oncogenes may also take place in some transformants, free of v-src activity.
authors.affiliation: Institute of Carcinogenesis, Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: G I
authors.initials: GI
authors.lastname: Deichman
authors.forename: L M
authors.initials: LM
authors.lastname: Kashkina
authors.forename: O A
authors.initials: OA
authors.lastname: Mizenina
authors.forename: E G
authors.initials: EG
authors.lastname: Gorojanskaya
authors.forename: M A
authors.initials: MA
authors.lastname: Nikiforov
authors.forename: A V
authors.initials: AV
authors.lastname: Gudkov
authors.forename: N A
authors.initials: NA
authors.lastname: Dyakova
authors.forename: A V
authors.initials: AV
authors.lastname: Komelkov
authors.forename: M O
authors.initials: MO
authors.lastname: Prilutskaya
authors.forename: N E
authors.initials: NE
authors.lastname: Kushlinsky
authors.forename: A G
authors.initials: AG
authors.lastname: Tatosyan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001358:Avian Sarcoma Viruses / Q000502:physiology*; D002374:Catalase / Q000378:metabolism*; D002417:Cattle; D002461:Cell Line, Transformed / Q000187:drug effects; D002472:Cell Transformation, Viral; D006224:Cricetinae; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D011905:Genes, ras; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017921:Mastadenovirus / Q000502:physiology; D008647:Mesocricetus; D009363:Neoplasm Proteins / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D018384:Oxidative Stress; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D013539:Simian virus 40 / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism*; D014162:Transfection
chemical_list: D000975:Antioxidants; D009363:Neoplasm Proteins; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D015688:Oncogene Protein pp60(v-src); D016283:Proto-Oncogene Proteins p21(ras); D005978:Glutathione