Biomarkers. 1997;2(1):17-24. doi: 10.1080/135475097231922.
Several authors have reported the high hepatic incidence of γhexachlorocyclohexane (γHCH), pentachlorophenol (PCP) and hexachlorobenzene (HCB) which are widely used as pesticides. Their genotoxicity status was not clearly known and no m utagenic effects, using the Salmonella assay, were reported. In the first part of this report, DNA-adduct form ation is evaluated in three types of cultured hepatic cells (rodent, bird and hum an) as a biomarker of exposure to genotoxic com pounds. γHCH-, PCP- and HCB-DNA adducts were analysed, using the sensitive (32)P-postlabelling assay in its nuclease P1 enrichm ent version. The genotoxicity of lindane and PCP is clearly established. Total DNA-adducts reached a m axim um in foetal rat hepatocytes (17 and 15 adducts per 10(9) nucleotides) after an exposure to pentachlorophenol and lindane respectively. After HCB treatm ent, lim ited am ounts of DNA-adducts were found in the different cells used. The finding that DNA adducts were not the sam e in all species tested m ight be due to m etabolic differences. Each type of cultured cells preferentially express different cytochrome P450 fam ilies. These P450s m etabolize a wide variety of xenobiotics and bioactivate carcinogens into reactive m etabolites able to form DNA-adducts. The objective of the present study was to exam ine the possible association between DNA-adduction and particular C YP450 induction. The induced cytochrom e P450s were m easured by northern blot analysis. In rat and hum an cells, lindane treatm ent strongly induces CYP2B and CYP3A m RNA levels, whereas pentachlorophenol treatm ent induces CYP1A, CYP2B and CYP3A.
一些作者报道了广泛用于农药的γ-六氯环己烷（γHCH）、五氯苯酚（PCP）和六氯苯（HCB）在肝脏中的高发生率。它们的遗传毒性状况尚不清楚，也没有报道使用沙门氏菌试验有诱变作用。在本报告的第一部分中，我们评估了三种类型的培养肝细胞（啮齿动物、鸟类和人类）中的 DNA 加合物形成情况，作为暴露于遗传毒性化合物的生物标志物。使用灵敏的（32）P-后标记法及其核酸酶 P1 富集版本分析了γHCH、PCP 和 HCB-DNA 加合物。林丹和 PCP 的遗传毒性是明确的。在接触五氯苯酚和林丹后，胎鼠肝细胞中的总 DNA 加合物达到最大值（分别为每 10（9）个核苷酸 17 和 15 个加合物）。在 HCB 处理后，在使用的不同细胞中仅发现有限量的 DNA 加合物。在所有测试的物种中，DNA 加合物并不相同，这可能是由于代谢差异所致。每种类型的培养细胞都优先表达不同的细胞色素 P450 家族。这些 P450 代谢各种外源性化学物质，并将致癌物质生物转化为能形成 DNA 加合物的反应性代谢物。本研究的目的是检查 DNA 加合与特定 CYP450 诱导之间可能存在的关联。通过 northern blot 分析测量诱导的细胞色素 P450。在大鼠和人类细胞中，林丹处理强烈诱导 CYP2B 和 CYP3A mRNA 水平，而五氯苯酚处理诱导 CYP1A、CYP2B 和 CYP3A。
