Formation of DNA adducts in vitro and in Salmonella typhimurium upon metabolic reduction of the environmental mutagen 1-nitropyrene
The polycyclic nitroaromatic hydrocarbon 1-nitropyrene is an environmental pollutant, a potent bacterial mutagen, and a carcinogen. Xanthine oxidase, a mammalian nitroreductase, catalyzed the in vitro metabolic activation of this compound to DNA-bound adducts. Maximum adduct formation occurred at pH 5.5 to 6.0 and was increased by the addition of catalase to the incubation medium. DNA binding from 1-nitropyrene was inhibited by hydrogen peroxide, L-ascorbate, and glutathione. Enzymatic hydrolysis of the modified DNA and subsequent analysis by high-pressure liquid chromatography indicated the presence of one major and two minor adducts. The major adduct was characterized by mass spectrometry and nuclear magnetic resonance spectroscopy as N-(deoxyguanosin-8-yl)-1-aminopyrene. The minor adducts appear to be decomposition products of the major adduct. When Salmonella typhimurium TA1538 was incubated with 1-nitropyrene, a strong correlation was found between the extent of DNA binding and the frequency of induced histidine reversions. Analysis of the bacterial DNA indicated one major adduct which had chromatographic properties and pKaS identical to those of N-(deoxyguanosin-8-yl)-1-aminopyrene. These data indicate that N-hydroxy-1-aminopyrene is probably the mutagenic and DNA-binding species formed during the metabolic reduction of 1-nitropyrene.
- Research Organization:
- National Center for Toxicological Research, Jefferson, Arkansas
- OSTI ID:
- 5852712
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 43:5; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560302* -- Chemicals Metabolism & Toxicology-- Microorganisms-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AROMATICS
BACTERIA
CHEMICAL BONDS
CHROMATOGRAPHY
DNA
IN VITRO
MAGNETIC RESONANCE
MASS SPECTROSCOPY
METABOLIC ACTIVATION
METABOLISM
MICROORGANISMS
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RESONANCE
SALMONELLA
SALMONELLA TYPHIMURIUM
SEPARATION PROCESSES
SPECTROSCOPY
STRUCTURAL CHEMICAL ANALYSIS