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• W1976831386 endingPage "1425" @default.
• W1976831386 startingPage "1419" @default.
• W1976831386 abstract "Base excision repair (BER) is the DNA repair pathway primarily responsible for repairing small base modifications and abasic sites caused by normal cellular metabolism or environmental insult. Strong evidence supports the requirement of DNA polymerase β (β-pol) in the BER pathway involving single nucleotide gap filling DNA synthesis in mammalian systems. In this study, we examine the relationship between oxidative stress, cellular levels of β-pol and BER to determine whether oxidizing agents can upregulate BER capacity in vivo . Intraperitoneal injection of 2-nitropropane (2-NP, 100 mg/kg), an oxidative stress-inducing agent, in C57BL/6 mice was found to generate 8-hydroxydeoxyguanosine (8-OHdG) in liver tissue (4-fold increase, P < 0.001). We also observed a 4–5-fold increase in levels of DNA single strand breaks in 2-NP treated animals. The protein level of the tumor suppressor gene, p53 was also induced in liver by 2-NP (2.1-fold, P < 0.01), indicating an induction of DNA damage. In addition, we observed a 2–3-fold increase in mutant frequency in the lacI gene after exposure to 2-NP. Interestingly, an increase in DNA damage upregulated the level of β-pol as well as BER capacity (42%, P < 0.05). These results suggest that β-pol and BER can be upregulated in response to oxidative stress in vivo . Furthermore, data show that heterozygous β-pol knockout (β-pol +/– ) mice express higher levels of p53 in response to 2-NP as compared with wild-type littermates. While the knockout and wild-type mice display similar levels of 8-OHdG after 2-NP exposure, the β-pol +/– mice exhibit a significant increase in DNA single strand breaks. These findings suggest that in mice, a reduction in β-pol expression results in a higher accumulation of DNA damage by 2-NP, thus establishing the importance of the β-pol-dependent BER pathway in repairing oxidative damage." @default.
• W1976831386 created "2016-06-24" @default.
• W1976831386 creator A5027592948 @default.
• W1976831386 date "2002-09-01" @default.
• W1976831386 modified "2023-09-27" @default.
• W1976831386 title "Induction of DNA polymerase beta-dependent base excision repair in response to oxidative stress in vivo" @default.
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• W1976831386 doi "https://doi.org/10.1093/carcin/23.9.1419" @default.
• W1976831386 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12189182" @default.
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