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

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 376卷 / 02期

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

页码：336 / 340

页数：5

共 28 条

[1] Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein [J].

Audebert, M ;

Radicella, JP ;

Dizdaroglu, M .

NUCLEIC ACIDS RESEARCH, 2000, 28 (14) :2672-2678

[2] The effect of p53-RNAi and p53 knockout on human 8-oxoguanine DNA glycosylase (hOgg1) activity [J].

Chatterjee, A ;

Mambo, E ;

Osada, M ;

Upadhyay, S ;

Sidransky, D .

FASEB JOURNAL, 2005, 19 (13) :112-+

[3] Oxidative DNA damage: mechanisms, mutation, and disease [J].

Cooke, MS ;

Evans, MD ;

Dizdaroglu, M ;

Lunec, J .

FASEB JOURNAL, 2003, 17 (10) :1195-1214

[4] Repair pathways for processing of 8-oxoguanine in DNA by mammalian cell extracts [J].

Dianov, G ;

Bischoff, C ;

Piotrowski, J ;

Bohr, VA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (50) :33811-33816

[5]

Dobson Allison W, 2002, Methods Mol Biol, V197, P351, DOI 10.1385/1-59259-284-8:351

[6] Role of inflammation in pancreatic carcinogenesis and the implications for future therapy [J].

Garcea, G ;

Dennison, AR ;

Steward, WP ;

Berry, DP .

PANCREATOLOGY, 2005, 5 (06) :514-529

[7] Cancer statistics, 2008 [J].

Jemal, Ahmedin ;

Siegel, Rebecca ;

Ward, Elizabeth ;

Hao, Yongping ;

Xu, Jiaquan ;

Murray, Taylor ;

Thun, Michael J. .

CA-A CANCER JOURNAL FOR CLINICIANS, 2008, 58 (02) :71-96

[8] Comparison of DNA adduct levels associated with oxidative stress in human pancreas [J].

Kadlubar, FF ;

Anderson, KE ;

Häussermann, S ;

Lang, NP ;

Barone, GW ;

Thompson, PA ;

MacLeod, SL ;

Chou, MW ;

Mikhailova, M ;

Plastaras, J ;

Marnett, LJ ;

Nair, J ;

Velic, I ;

Bartsch, H .

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1998, 405 (02) :125-133

[9] DNA adducts, genetic polymorphisms, and K-ras mutation in human pancreatic cancer [J].

Li, DH ;

Firozi, PF ;

Zhang, WQ ;

Shen, JJ ;

DiGiovanni, J ;

Lau, S ;

Evans, D ;

Friess, H ;

Hassan, M ;

Abbruzzese, JL .

MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2002, 513 (1-2) :37-48

[10] Oxidative DNA damage and 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase in human breast cancer [J].

Li, DH ;

Zhang, WQ ;

Zhu, JJ ;

Chang, P ;

Sahin, A ;

Singletary, E ;

Bondy, M ;

Mitra, S ;

Lau, SS ;

Shen, JJ ;

DiGiovanni, J .

MOLECULAR CARCINOGENESIS, 2001, 31 (04) :214-223

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