title: Comparative direct-acting mutagenicity of 1- and 2-nitropyrene: evidence for 2-nitropyrene mutagenesis by both guanine and adenine adducts.
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.
authors.affiliation: National Center for Toxicological Research, Jefferson, AR 72079.
authors.forename: S Y
authors.initials: SY
authors.lastname: Yu
authors.forename: R H
authors.initials: RH
authors.lastname: Heflich
authors.forename: L S
authors.initials: LS
authors.lastname: Von Tungeln
authors.forename: K
authors.initials: K
authors.lastname: el-Bayoumy
authors.forename: F F
authors.initials: FF
authors.lastname: Kadlubar
authors.forename: P P
authors.initials: PP
authors.lastname: Fu
mesh_terms: D000225:Adenine / Q000737:chemistry; D004249:DNA Damage; D006147:Guanine / Q000737:chemistry; D009152:Mutagenicity Tests; D009153:Mutagens; D011721:Pyrenes / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000235:genetics
chemical_list: D009153:Mutagens; D011721:Pyrenes; D006147:Guanine; C049029:2-nitropyrene; D000225:Adenine; C032668:1-nitropyrene