Deichman G I, Kashkina L M, Mizenina O A, Gorojanskaya E G, Nikiforov M A, Gudkov A V, Dyakova N A, Komelkov A V, Prilutskaya M O, Kushlinsky N E, Tatosyan A G
Institute of Carcinogenesis, Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russia.
Int J Cancer. 1996 Jun 11;66(6):747-52. doi: 10.1002/(SICI)1097-0215(19960611)66:6<747::AID-IJC7>3.0.CO;2-#.
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.
我们先前已证明，经劳氏肉瘤病毒施密特 - 鲁平株（RSV - SR）转化的仓鼠胚胎成纤维细胞（HEF）对H2O2损伤具有高度抗性（H2O2R）（与自发转化、或经牛腺病毒和SV40转化的HEF形成对比），而RSV - SR转化体的N - ras转染导致pp6Ov - scr和H2O2R受到抑制。在本研究中，我们研究了（1）经这些因子转化的HEF的抗氧化活性（AOA）机制，以及（2）v - src基因在RSV - SR转化体异常高的AOA中可能发挥的作用，以及活化的ras癌基因在其抑制过程中可能发挥的作用。所有转化体的过氧化氢酶和谷胱甘肽过氧化物酶（GP）活性均增加，而超氧化物歧化酶（SOD）、谷胱甘肽和谷胱甘肽还原酶（GR）则减少。与其他转化体相比，过氧化氢酶显著更高且SOD活性较低是RSV - SR转化体的特征，而在所有类型的转化体中均观察到GP增加。相应地，RSV - SR转化体表现出极高的H2O2分解活性（H2O2CA）且无脂质过氧化链反应（LPCR）。N - ras诱导的RSV - SR转化的HEF的pp60v - scr抑制与过氧化氢酶、GP、H2O2和H2O2CA的抑制同时发生。然而，在N - ras和Ha - ras转染的、自发转化的HEF中也观察到过氧化氢酶和GP的抑制。因此，极高的过氧化氢酶活性和LPCR的抑制显然是RSV - SR转化体异常高的H2O2R的主要机制，而其被活化的ras癌基因抑制也可能在一些无v - src活性的转化体中发生。
