5-Methylchrysene metabolism in mouse epidermis in vivo, diol epoxide--DNA adduct persistence, and diol epoxide reactivity with DNA as potential factors influencing the predominance of 5-methylchrysene-1,2-diol-3,4-epoxide--DNA adducts in mouse epidermis

Journal Article · Fri Dec 31 23:00:00 EST 1982 · Carcinogenesis (N.Y.); (United States)

DOI:https://doi.org/10.1093/carcin/4.7.843· OSTI ID:5532693

Melikian, A A; LaVoie, E J; Hecht, S S; Hoffmann, D

5-Methylchrysene (5-MeC) can form two bay region dihydrodiol epoxides: 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I) which has the methyl group and the epoxide ring in the same bay region, and 7,8-dihydroxy-9,10-epoxy-7,8,10-tetrahydro-5-methylchrysene (DE-II). In a previous study, we observed that the ratio of DE-I:DNA adducts to DE-II:DNA adducts in mouse epidermis, 24 h after application of (/sup 3/H)5-MeC metabolites was 2.7 to 1. To investigate the basis for this observation we have now studies: (i) the formation of (/sup 3/H)5-MeC in mouse epidermis in vivo at various time intervals from 0.33 to 24 h; (ii) the persistence of DE-I:DNA adducts and DE-II:DNA adducts in mouse epidermis at 4-48 h after application of (/sup 3/H)5-MeC; and (iii) the reactions of DE-I and DE-II with calf thymus DNA in vitro. In contrast to results obtained with mouse liver 9000 grams supernatant, the dihydrodiol precursors of DE-I and DE-II were present in equivalent quantities in mouse epidermis in vivo at every time point studied. The ratio of DE-I:DNA adducts to DE-II:DNA adducts in mouse epidermis was constant throughout the time period studied. However, the extent of formation of DE-I:DNA adducts was greater than that of DE-II:DNA adducts upon reaction of DE-I or DE-II with calf thymus DNA in vitro. These results suggest that differences in reactivity with DNA of DE-I and DE-II may bw responsible for the higher levels in mouse epidermis of DE-I:DNA adducts compared with DE-II:DNA adducts and provide a possible basis for the observed enhancing effect of a bay region methyl group on the carcinogenicity of polynuclear aromatic hydrocarbons.

• Research Organization: Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY
• OSTI ID: 5532693
• Journal Information: Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 4:7; ISSN CRNGD
• 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.
ADDUCTS
ANIMAL TISSUES
ANIMALS
AROMATICS
BODY
CARCINOGENS
CHEMICAL BONDS
CHRYSENE
CONDENSED AROMATICS
DNA
DNA ADDUCTS
EPIDERMIS
EPITHELIUM
EPOXIDES
FEMALES
HYDROCARBONS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
METABOLITES
MICE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
RODENTS
SKIN
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES