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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

  • Kim, Byung-Wook (Department of Biochemistry, College of Natural Sciences, Yeungnam University) ;
  • Kim, Byung-Chun (Department of Biochemistry, College of Natural Sciences, Yeungnam University) ;
  • Cha, Jin-Soon (Department of Chemistry, College of Natural Sciences, Yeungnam University) ;
  • Pfeifer, Gerd P. (Department of Biology, Beckman Research Institute of the City of Hope) ;
  • Lee, Chong-Soon (Department of Biochemistry, College of Natural Sciences, Yeungnam University)
  • Published : 2008.08.31

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 $G{\rightarrow}A$ transitions, $G{\rightarrow}C$ transversions, and $G{\rightarrow}T$ transversions. In the case of 1-nitropyrene 9,10-oxide, $G{\rightarrow}A$ transitions, $G{\rightarrow}T$ transversions, $A{\rightarrow}G$ transitions and $G{\rightarrow}C$ 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.

Keywords

References

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