Deficient repair of 8-hydroxyguanine in the BxPC-3 pancreatic cancer cell line

被引:5
作者
Nyaga, Simon G. [1 ]
Lohani, Althaf [1 ]
Evans, Michele K. [1 ]
机构
[1] NIA, Cellular & Mol Biol Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA
关键词
Pancreatic cancer; Oxidative stress; Oxidative DNA damage; DNA repair; Base excision repair; Reactive oxygen species; 8-Hydroxyguanine; hOGG1; Pancreatic cancer risk and antioxidant enzymes;
D O I
10.1016/j.bbrc.2008.08.134
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Elevated levels of oxidatively induced DNA lesions have been reported in malignant pancreatic tissues relative to normal pancreatic tissues. However, the ability of the pancreatic cancer cells to remove these lesions has not previously been addressed. This study analyzed the effectiveness of the pancreatic cancer cell line, BxPC-3 to repair 8-hydroxyguanine (8-OH-Gua) relative to a nonmalignant cell line. We show that BxPC-3 cells repair 8-OH-Gua less effectively than the nonmalignant cells. This repair deficiency correlated with significant downregulation of the hOGG1 protein and the corresponding mRNA (30-fold lower than GAPDH) in BxPC-3 cell line. The repair defect was complemented in vivo by transient transfection of the hOGG1 gene and in vivo by recombinant hOGG1. These results are the first to show a deficiency of 8-OH-Gua repair in BxPC-3 cells, implicating this defect in the risk factor of pancreatic cancer. Published by Elsevier Inc.
引用
收藏
页码:336 / 340
页数:5
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