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KMID : 0624620080410080604
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BMB Reports
2008 Volume.41 No. 8 p.604 ~ p.608
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Mutation spectra induced by 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide in the supF gene of human XP-A fibroblasts
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Kim Byung-Wook
Kim Byung-Chun
Cha Jin-Soon
Pfeifer Gerd P.
Lee Chong-Soon
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Abstract
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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.
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KEYWORD
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Mutagenicity, 1-Nitropyrene 4, 5-Oxide, 1-Nitropyrene 9, 10-Oxide, Shuttle vector plasmid pSP189, supF gene
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