A STUDY OF CHEMICAL CARCINOGENESIS .39. INFLUENCE OF A BAY-REGION METHYL-GROUP ON FORMATION OF 5-METHYLCHRYSENE DIHYDRODIOL EPOXIDE-DNA ADDUCTS IN MOUSE SKIN

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (4) , 1239-1242
Abstract
The binding [3H], 5-methylchrysene to DNA of CD-1 mouse skin 24 h after treatment was studied. DNA was isolated from the treated skin areas of mice and hydrolyzed enzymatically to deoxyribonucleosides, and the hydrolysate was chromatographed on a Sephadex LH-20 column using a methanol:water gradient. The major adducts eluted between 70-100 ml (Peak 1), 470-590 ml (Peaks 2A to C) and 750-850 ml (Peak 3). For identification of these products, markers were prepared from 5-methylchrysene bay-region dihydrodiol epoxides. [5-14C]1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene and [5-14C]7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene were synthesized by reacting the corresponding metabolically formed [5-14C]1,2-dihydro-1,2-dihydroxy-5-methylchrysene and [5-14C]7,8-dihydro-7,8-dihydroxy-5-methylchrysene with m-chloroperoxybenzoic acid. The structures of the dihydrodiol epoxides were established by their mass spectra and by hydrolysis to tetrols. Peak 2B was chromatographically indistinguishable on Sephadex LH-20 and reverse-phase high-pressure liquid chromatography from the adduct formed when [5-14C]1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methyl-chrysene was reacted with salmon sperm DNA in solution. Peak 2A was chromatographically inseparable from the [5-14C]7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene:DNA adduct. Adduct 2B was formed to a greater extent than adduct 2A by the ratio of 2.7:1. 5-Methylchrysene apparently preferentially forms DNA adducts from the bay-region dihydrodiol epoxide adjacent to the methyl group. [Methylated polynuclear aromatic hydrocarbons are important environmental carcinogens.].

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