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.
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.
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小鼠表皮中的 5-甲基体内代谢、二醇环氧化物 - DNA 加合物的持久性以及二醇环氧化物与 DNA 的反应性作为影响 5-甲基 - 1,2-二醇-3,4-环氧化物 - DNA 加合物优势的潜在因素
DOI：
10.1093/carcin/4.7.843
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发表时间：
1983
期刊：
影响因子：
4.7
通讯作者：
Hoffmann,D
中科院分区：
文献类型：
--
作者：
Melikian,AA;LaVoie,EJ;Hecht,SS;Hoffmann,D
5-5-MeC可以形成两个湾区二氢二醇环氧化物：1，2-二羟基-3-4-环氧-1，2，3，4-四氢-5-甲基喹啉（DE-I），它的甲基和环氧环在同一湾区;在先前的研究中，我们观察到在施用[3H] 5-MeC代谢物后24小时，小鼠表皮中DE-I：DNA加合物与DE-II：DNA加合物的比率为2.7：1。为了研究这一观察结果的基础，我们现在研究了：（i）[3H] 5-MeC在小鼠表皮内0.33至24小时不同时间间隔的形成;（ii）DE-I：DNA加合物和DE-II：DNA加合物在小鼠表皮内应用[3H] 5-MeC后4 - 48小时的持续性;（iii）DE-I和DE-II与小牛胸腺DNA的体外反应。与用小鼠肝脏9000 g上清液获得的结果相反，DE-I和DE-II的二氢二醇前体在研究的每个时间点均以等量存在于小鼠体内表皮中。DE-I：DNA加合物与DE-II：DNA加合物在小鼠表皮中的比例在整个研究时间段内是恒定的。但DE-I或DE-II与小牛胸腺DNA在体外反应时，形成DE-I：DNA加合物的程度大于DE-II：DNA加合物的程度。这些结果表明，DE-I和DE-II与DNA的反应性的差异可能是负责在小鼠表皮的DE-I：DNA加合物与DE-II：DNA加合物相比，更高的水平，并提供了一个可能的基础上观察到的海湾地区的甲基对多核芳烃的致癌性的增强作用。
5-Methylcbrysene (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-7,8,9,10-tetrahydro-5-methylchrysene (DE-II). In a previous study, we observed that the ratio of DE-I:DNA adduds to DE-II:DNA adducts in mouse epidermis, 24 h after application of [3H]5-MeC metabolites was 2.7 to 1. To investigate the basis for this observation we have now studied: (i) the formation of [3H]5-MeC in mouse epidermisin vivoat 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 [3H]5-MeC and (iii) the reactions of DE-I and DE-II with calf thymus DNAin vitro. In contrast to results obtained with mouse liver 9000 g supernatant, the dihydrodiol precursors of DE-I and DE-II were present in equivalent quantities in mouse epidermisin vivoat 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 DNAin vitro. These results suggest that differences in reactivity with DNA of DE-I and DE-II may be 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.
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影响因子：
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作者：
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DOI：
--
发表时间：
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期刊：
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J. Mellanby
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影响因子：
2.9
作者：
DISCIPIO, RG;HERMODSON, MA;DAVIE, EW
通讯作者：
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