Seree E M, Villard P H, Re J L, De Meo M, Lacarelle B, Attolini L, Dumenil G, Catalin J, Durand A, Barra Y
URA CNRS 1924, EA 859: Laboratoire de Pharmacocinétique et de Toxicologie, Faculté de Médicine, Marseille, France.
Biochem Biophys Res Commun. 1996 Feb 15;219(2):429-34. doi: 10.1006/bbrc.1996.0250.
Several studies have shown in humans an association between renal carcinoma and cigarette smoking. Cigarette smoke contains numerous cytochrome P450 inducers and substrates. In the present study we investigated the effect of cigarette smoke on the regulation of murine cytochrome P450 expression in kidney and its possible role in the induction of single strand breaks in DNA. Results demonstrated that CYP2E1 (activity, protein, and MRNA) was induced by tobacco smoke (2.1, 5.6 and 20.8, respectively). We did not detect any CYP1A, CYP2B, and CYP3A using Western blot and RT-PCR experiments. We have analyzed the renal single strand breaks of DNA in control and treated mice. The results indicated an increase of single strand breaks of DNA in kidney from treated mice which paralleled the high inducibility of the CYP2E1. No significant difference was observed between lymphocytes (which expressed very low or undetectable cytochrome P450 levels) of control and treated mice.
多项研究表明，在人类中肾癌与吸烟之间存在关联。香烟烟雾含有多种细胞色素P450诱导剂和底物。在本研究中，我们调查了香烟烟雾对小鼠肾脏中细胞色素P450表达调控的影响及其在诱导DNA单链断裂中的可能作用。结果表明，CYP2E1（活性、蛋白质和mRNA）分别被烟草烟雾诱导了2.1倍、5.6倍和20.8倍。我们通过蛋白质印迹和逆转录聚合酶链反应实验未检测到任何CYP1A、CYP2B和CYP3A。我们分析了对照小鼠和处理小鼠肾脏中的DNA单链断裂情况。结果表明，处理小鼠肾脏中DNA单链断裂增加，这与CYP2E1的高诱导性平行。对照小鼠和处理小鼠的淋巴细胞（表达极低或无法检测到的细胞色素P450水平）之间未观察到显著差异。
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