Identification of the Major Adducts Formed by Reaction of 5-Methylchrysene Anti-Dihydrodiol-Epoxides with DNA in Vitro

Assieh A. Melikian, Shantu Amin, Stephen S. Hecht, Dietrich Hoffmann, John Pataki, Ronald G. Harvey

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

5-Methylchrysene is metaboiically converted to the bay-re-gion dihydrodiol-epoxides, trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DEI), in which the methyl group and the epoxide ring are in the same bay region, and frans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methytchrysene (DE-II). Previous studies have indicated that DEI is more important in 5-methylchrysene carcinogenesis than is DE-II. Both DE-I and DE-II were individually reacted with calf thymus DNA in vitro. The DNA was enzymatically hydrolyzed to deoxyribonudeosides, and the modified deoxyribonudeosides were separated by chromatography on Sephadex LH-20 and analyzed by high-performance liquid chromatography. One major adduct and seven minor adducts were formed from each dihy-drodiol-epoxide. The major adduct was, in each case, characterized by its pH-dependent partition coefficient, stability to base, mass spectrum, ultraviolet spectrum, and nuclear magnetic resonance spectrum as a deoxyguanosine derivative resulting from addition of the exocydic amino group of deoxyguanosine to the benzyiic carbon of the epoxide ring of the dihydrodiol-epoxide. The results of this study show that the major DNA adducts formed from 5-methylchrysene via DEI and DE-II are structurally similar.

Original languageEnglish (US)
Pages (from-to)2524-2529
Number of pages6
JournalCancer Research
Volume44
Issue number6
StatePublished - Jun 1 1984

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