Covalent DNA adducts formed in mouse epidermis by benzo[g]chrysene

被引:20
作者
Giles, AS
Seidel, A
Phillips, DH
机构
[1] INST CANC RES, HADDOW LABS, SUTTON SM2 5NG, SURREY, ENGLAND
[2] UNIV MAINZ, INST TOXICOL, D-6500 MAINZ, GERMANY
关键词
D O I
10.1093/carcin/17.6.1331
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The metabolic activation in mouse skin of benzo[g]chrysene (B[g]C), a moderately carcinogenic polycyclic aromatic hydrocarbon (PAH) present in coal tar, was investigated, Male Parkes mice were treated topically with 0.5 mu mol B[g]C and DNA was isolated from the treated areas of skin at various times after treatment and analysed by P-32-postlabelling, Seven major adduct spots were detected, at a maximum level of 6.55 fmol adducts/mu g DNA, Mouse skin treated with the PAH benzo[c]phenanthrene (B[c]Ph) gave a total of 0.24 fmol adducts/mu g DNA, B[g]C-DNA adducts persisted in skin for at least 3 weeks, Treatment of mice with 0.5 mu mol of the optically pure putative proximate carcinogens, the (+)- and (-)-trans benzo[g]chrysene-11,12-dihydrodiols, led to the formation of adducts which comigrated on TLC and HPLC with those formed in B[g]C-treated mice, which suggested that the detected adducts were formed by the fjord region B[g]C-11,12-dihydrodiol-13,14-epoxides (B[g]CDEs). To test this, the four optically pure synthetic B[g]CDEs were reacted in vitro with DNA and the heteroco-polymers poly(dA . dT) and poly(dG . dC) and these samples P-32-postlabelled. Co-chromatography, on both TLC and HPLC, of lit vitro and in vivo adducts indicated that B[g]C is activated in mouse skin through formation of the (-)-anti-(11R,12S,13S,14R) and (+)-syn-(11S,12R,13S,14R) B[g]CDEs, (-)-anti-B[g]CDE formed five adducts with DNA, two of them with adenine and three with guanine bases, (+)-syn-B[g]CDE formed one adduct with each of these bases in DNA, The adenine adducts accounted for 64% of the total major adducts formed in B[g]C-treated mouse skin. The route of metabolic activation of B[g]C is similar to that reported for B[c]Ph, but the extent of activation to the fjord region diol-epoxides is significantly greater in the case of B[g]C, as demonstrated by the higher levels of adduct formation in vivo.
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页码:1331 / 1336
页数:6
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