Identification of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene as a major mutagenic metabolite of 6-nitrochrysene. [Salmonella typhimurium; rats]
Liver 9000 X g supernatant from rats was used to study the metabolism of (6- /sup 14/C)nitrochrysene under aerobic conditions. The major ethyl acetate-soluble metabolite (1.06 nmol/mg of protein in 30 min) was identified as 1,2-dihydro-1,2-dihydroxy-6-nitrochrysene, based on its mass, UV, and proton magnetic resonance spectra. Under aerobic conditions, 6-aminochrysene was not detected as a metabolite. However, when incubations were carried out in an atmosphere of 4% O/sub 2/ in N/sub 2/, both 1,2-dihydro-1,2-dihydroxy-6-nitrochrysene (0.04 nmol/mg of protein) and 6-aminochrysene (0.05 nmol/mg of protein) were detected. Further metabolism of the /sup 14/C-labeled 1,2-dihydro-1,2-dihydroxy-6-nitrochrysene by rat liver 9000 X g supernatant under aerobic conditions gave a major metabolite which was identified tentatively as 1,2-dihydroxy-6-nitrochrysene. The mutagenic activities of 6-nitrochrysene, trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene and 6-aminochrysene were assessed in Salmonella typhimurium strains TA100 and TA98. In the absence of rat liver 9000 X g supernatant, trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene was the more potent mutagen in TA100 but, in TA98, it was less active than was 6-nitrochrysene. In the presence of rat liver 9000 X g supernatant, both trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene and 6-nitrochrysene were more mutagenic in TA100 than in the assays performed without an activating system, and the dihydrodiol metabolite was more mutagenic than was 6-nitrochrysene. In TA98 with activation, trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene, 6-aminochrysene, and 6-nitrochrysene were all mutagenic. The results of this study indicate that trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene is a major proximate mutagen of 6-nitrochrysene in S. typhimurium TA100.
- Research Organization:
- Naylor Dana Inst. for Disease Prevention, Valhalla, NY
- OSTI ID:
- 6304766
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 44:8; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AEROBIC CONDITIONS
ANIMALS
AROMATICS
BACTERIA
BODY
CARBON 14 COMPOUNDS
CHRYSENE
CONDENSED AROMATICS
DIGESTIVE SYSTEM
GLANDS
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLIC ACTIVATION
METABOLISM
METABOLITES
MICROORGANISMS
MUTAGEN SCREENING
MUTAGENESIS
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RATS
RODENTS
SALMONELLA
SALMONELLA TYPHIMURIUM
SCREENING
TRACER TECHNIQUES
VERTEBRATES