Repair of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA pyridyloxobutylation by nucleotide excision repair.
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.
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont., Canada K7L 3N6.
Pamela J
PJ
Brown
Leanne L
LL
Bedard
Thomas E
TE
Massey
D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects; D018736:DNA Adducts / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009602:Nitrosamines / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity; D013997:Time Factors; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics / Q000378:metabolism
D002273:Carcinogens; D018736:DNA Adducts; D004268:DNA-Binding Proteins; D009602:Nitrosamines; D011725:Pyridines; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C081510:4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone; C086984:XPC protein, human; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone