title: Mutation spectra induced by 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide in the supF gene of human XP-A fibroblasts.
abstract: 1-Nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide are oxidative metabolites that are responsible for the mutagenicity of 1-nitropyrene. In this study, the mutation spectra induced by oxidative metabolites in human cells were determined using a shuttle vector assay. The mutation frequencies induced by 1-nitropyrene 9,10-oxide were 2-3 times higher than those induced by 1-nitropyrene 4,5-oxide. The base substitutions induced by 1-nitropyrene 4,5-oxide were G --> A transitions, G --> C transversions, and G --> T transversions. In the case of 1-nitropyrene 9,10-oxide, G --> A transitions, G --> T transversions, A --> G transitions and G --> C transversions were observed. Most base substitution mutations induced by oxidative metabolites occurred at the guanine sites in the supF gene. These sequence-specific hot spots were commonly identified as 5'-GA sequences for both metabolites. On the other hand, the sequence-specific hot spots at the adenine sites were identified as 5'-CAC sequences for 1-nitropyrene 9,10-oxide. These results suggest that the oxidative metabolites of 1-nitropyrene induce sequence-specific DNA mutations at the guanine and adenine sites at high frequency.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Yeungnam University, Gyeongsan 712-749, Korea.
authors.forename: Byung-Wook
authors.initials: BW
authors.lastname: Kim
authors.forename: Byung-Chun
authors.initials: BC
authors.lastname: Kim
authors.forename: Jin Soon
authors.initials: JS
authors.lastname: Cha
authors.forename: Gerd P
authors.initials: GP
authors.lastname: Pfeifer
authors.forename: Chong-Soon
authors.initials: CS
authors.lastname: Lee