Repair of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA pyridyloxobutylation by nucleotide excision repair

• Published in: Cancer letters Vol. 260; no. 1; pp. 48 - 55
• Main Authors: Brown, Pamela J, Bedard, Leanne L, Massey, Thomas E
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 18.02.2008; Elsevier Limited
• Subjects: Bioactivation; Cancer; Carbon; Carcinogens - toxicity; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - enzymology; Cell Nucleus - radiation effects; Cell Survival - drug effects; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA adducts; DNA Adducts - metabolism; DNA methylation; DNA Repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Genes; Genomes; Hematology, Oncology and Palliative Medicine; Humans; Medical research; Nitrosamines - toxicity; NNK; Nucleotide excision repair; Proteins; Pyridines - toxicity; Pyridyloxobutylation; Time Factors; Tobacco smoke; Ultraviolet Rays; Xeroderma Pigmentosum - enzymology; Xeroderma Pigmentosum - genetics; Xeroderma Pigmentosum - pathology; Xeroderma Pigmentosum Group A Protein - genetics; Xeroderma Pigmentosum Group A Protein - metabolism; TCR; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; Pyridyloxobutylation; Bioactivation; SPE; NNK; 4-methylnitrosamino-1-(3-pyridyl)-1-butanone; 4-(3-pyridyl)-4-oxobut-1-yl; NNAL; transcription-coupled repair; O 2-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine; 7-POB-Gua; global genome repair; O 2-[4-(3-pyridyl)-4-oxobut-1-yl]cytosine; solid phase extraction; POB; O 2-POB-Cyt; NNKOAc; O 6-POB-dGuo; 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine; 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone; GGR; O 2-POB-dThd; NER; HPB; DNA adducts; O 6-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxyguanosine; 4-hydroxy-1-(3-pyridyl)-1-butanone; nucleotide excision repair; Nucleotide excision repair
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2007.10.015

Abstract The tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) forms DNA methylating and pyridyloxobutylating species. In this study, the involvement of nucleotide excision repair (NER) in the repair of pyridyloxobutyl adducts was assessed using an in vitro NER assay with pyridyloxobutylated plasmid DNA. Nuclear extracts from NER-deficient xeroderma pigmentosum (XP) cells, XPA and XPC, were less active at repairing pyridyloxobutyl adducts than were extracts from normal cells, while combining NER-deficient extracts reconstituted activity. Also, NER-deficient cells were more susceptible to NNKOAc-induced cytotoxicity than were normal cells. Results demonstrate a role for NER in the repair of NNK-induced pyridyloxobutylation.