Identification of the major metabolites and DNA adducts formed from 2-nitropyrene in vitro

Carcinogenesis. 1991 Mar;12(3):475-9. doi: 10.1093/carcin/12.3.475.

Abstract

In contrast to 1-nitropyrene (1-NP), which is the most abundant nitropolycyclic aromatic hydrocarbon in numerous environmental sources, 2-nitropyrene (2-NP) has been detected only in the ambient air and not in direct emissions. Thus, 2-NP can be used as an indicator for monitoring human exposure to nitropolynuclear aromatic hydrocarbons in ambient air. Therefore, it is essential to determine the possible metabolic pathways of 2-NP. The metabolism of 2-NP by rat liver 9000 g supernatant was investigated. Under aerobic conditions, ring oxidation to 6-hydroxy-2-nitropyrene and nitroreduction to 2-aminopyrene (2-AP) were observed. When incubations were carried out in an atmosphere of nitrogen, 2-AP was the only metabolite detected. These results are consistent with those observed with 1-NP. In vitro metabolic activation of 2-NP to DNA adducts catalyzed by xanthine oxidase was also examined. Two adducts were characterized as N-(deoxyguanosin-8-yl)-2-aminopyrene and N-(deoxyadenosin-8-yl)-2-aminopyrene. The presence of deoxyadenosine adduct, which is derived from the nitroreduction pathway, may contribute to the powerful direct-acting mutagenicity of 2-NP.

Publication types

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

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods
  • DNA / metabolism*
  • Liver / metabolism
  • Male
  • Pyrenes / metabolism*
  • Rats
  • Rats, Inbred F344

Substances

  • Pyrenes
  • 2-nitropyrene
  • DNA