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• W4293508265 endingPage "908" @default.
• W4293508265 startingPage "869" @default.
• W4293508265 abstract "Cigarette smoke causes direct oxidative DNA damage as well as indirect damage through inflammation. Epidemiological studies show a strong relationship between secondhand smoke and cancer; however, the mechanisms of secondhand smoke-induced cancer are not well understood. Animal models with either (i) deficient oxidative DNA damage repair, or (ii) a decreased capacity to combat oxidative stress may help determine the pathways important in mitigating damage caused by smoke. In this study, we used mice lacking Ogg1 and Myh, both of which are involved in base excision repair by removing oxidatively damaged DNA bases. Gclm-deficient mice, which have decreased levels of glutathione (GSH), were used to look at the role of smoke-induced oxidative damage. Ex vivo experiments show significantly elevated levels of DNA single-strand breaks and chromosomal aberrations in peripheral blood lymphocytes from Ogg1−/−Myh−/− double knockout mice compared to wild type (WT) mice after 24 h of exposure to cigarette smoke extract (CSE). The average γH2AX foci per cell was significantly elevated 3 h after exposure to CSE in cells from Ogg1−/−Myh −/− double knockout mice compared to wildtype mice. In vivo we found that all mice had increased markers of DNA damage after exposure to side-stream tobacco smoke (SSTS). Ogg1−/−Myh−/− and Gclm−/− mice had altered levels of peripheral blood glutathione after SSTS exposure whereas wild type mice did not. This may be due to differential regulation of glutathione synthesis in the lung. We also found that Ogg1−/−Myh−/− mice had a decreased lifespan after oral gavage with benzo[a]pyrene compared to wildtype mice and sham-exposed Ogg1−/−Myh−/− mice. Our results are important in investigating the roles of oxidative stress and oxidative DNA damage repair in cigarette smoke-induced cancers and characterizing the role of genetic polymorphisms in smoke-related disease susceptibility." @default.
• W4293508265 created "2022-08-30" @default.
• W4293508265 creator A5056058103 @default.
• W4293508265 date "1993-11-01" @default.
• W4293508265 modified "2023-09-29" @default.
• W4293508265 title "NEUROLOGIC DISEASE IN SJOGREN’S SYNDROME: MONONUCLEAR INFLAMMATORY VASCULOPATHY AFFECTING CENTRAL/PERIPHERAL NERVOUS SYSTEM AND MUSCLE" @default.
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