Lévay G, Bodell W J
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143-0520.
Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7105-9. doi: 10.1073/pnas.89.15.7105.
Using P1 nuclease enhanced 32P postlabeling, we investigated DNA adduct formation in HL-60 promyelocytic leukemia cells treated with the benzene metabolites hydroquinone, catechol, and 1,2,4-benzenetriol. Comparison of the slopes of the dose-response curves showed that hydroquinone was 7-9 times more effective than 1,2,4,-benzenetriol and catechol at inducing DNA adducts. Comparison of hydroquinone with catechol showed a good correlation between adduct formation and cytotoxicity. Similar comparisons of hydroquinone and 1,2,4,-benzenetriol suggest that cellular processes in addition to DNA adduct formation contributed to cytotoxicity. In cells treated with the combination of hydroquinone and either catechol or 1,2,4,-benzenetriol, DNA adduct formation was 3-6 times greater than the sum of adduct formation produced by single-agent treatments. Treatment with hydroquinone and 1,2,4,-benzenetriol produced DNA adducts not detected after treatment with either metabolite alone. The synergistic interaction of benzene metabolites in the production of DNA adducts may play an important role in the genotoxic effects of benzene in vivo.
利用P1核酸酶增强的32P后标记法，我们研究了用苯代谢物对苯二酚、儿茶酚和1,2,4 -苯三酚处理的HL - 60早幼粒细胞白血病细胞中DNA加合物的形成。剂量反应曲线斜率的比较表明，在诱导DNA加合物方面，对苯二酚的效果比1,2,4 -苯三酚和儿茶酚高7 - 9倍。对苯二酚与儿茶酚的比较表明，加合物形成与细胞毒性之间存在良好的相关性。对苯二酚和1,2,4 -苯三酚的类似比较表明，除了DNA加合物形成外，细胞过程也对细胞毒性有贡献。在用对苯二酚与儿茶酚或1,2,4 -苯三酚联合处理的细胞中，DNA加合物的形成比单药处理产生的加合物形成总和大3 - 6倍。用对苯二酚和1,2,4 -苯三酚处理产生的DNA加合物在用任何一种代谢物单独处理后均未检测到。苯代谢物在DNA加合物产生中的协同相互作用可能在苯在体内的遗传毒性作用中起重要作用。
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