Comparative direct-acting mutagenicity of 1- and 2-nitropyrene: evidence for 2-nitropyrene mutagenesis by both guanine and adenine adducts

Mutat Res. 1991 Sep-Oct;250(1-2):145-52. doi: 10.1016/0027-5107(91)90170-s.

Abstract

The mutations and DNA adducts produced by the environmental pollutant 2-nitropyrene were examined in Salmonella typhimurium tester strains. 2-Nitropyrene was a stronger mutagen than its extensively studied structural isomer 1-nitropyrene in strains TA96, TA97, TA98, TA100, TA102, TA104 and TA1538. Both 1- and 2-nitropyrene were essentially inactive in TA1535. The mutagenicity of 1- and 2-nitropyrene in TA98 was much higher than in TA98NR and the activity of these compounds in TA100 was much higher than in TA100NR. While 1-nitropyrene exhibited similar mutagenicity in strains TA98 and TA98/1,8-DNP6, the mutagenicity of 2-nitropyrene in TA98/1,8-DNP6 was much lower than in TA98. Analysis of DNA from TA96 and TA104 incubated with 2-nitropyrene indicated the presence of two adducts, N-(deoxyguanosin-8-yl)-2-aminopyrene and N-(deoxyadenosin-8-yl)-2-aminopyrene. The results suggest that 2-nitropyrene is metabolized by bacterial nitroreductase(s) to N-hydroxy-2-aminopyrene, and possibly by activation to a highly mutagenic O-acetoxy ester. DNA adduct formation with deoxyguanosine and deoxyadenosine correlates with the mutagenicity of 2-nitropyrene in tester strains possessing both G:C and A:T mutational targets.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / chemistry
  • DNA Damage*
  • Guanine / chemistry
  • Mutagenicity Tests
  • Mutagens*
  • Pyrenes / toxicity*
  • Salmonella typhimurium / genetics

Substances

  • Mutagens
  • Pyrenes
  • Guanine
  • 2-nitropyrene
  • Adenine
  • 1-nitropyrene