TY - JOUR
T1 - Identification of the Major Adducts Formed by Reaction of 5-Methylchrysene Anti-Dihydrodiol-Epoxides with DNA in Vitro
AU - Melikian, Assieh A.
AU - Amin, Shantu
AU - Hecht, Stephen S.
AU - Hoffmann, Dietrich
AU - Pataki, John
AU - Harvey, Ronald G.
PY - 1984/6/1
Y1 - 1984/6/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 6547075
AN - SCOPUS:0021139865
SN - 0008-5472
VL - 44
SP - 2524
EP - 2529
JO - Cancer Research
JF - Cancer Research
IS - 6
ER -