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首页> 外文期刊>Toxicologic pathology >Comparison of the levels of enzymes involved in drug metabolism between transgenic or gene-knockout and the parental mice.
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Comparison of the levels of enzymes involved in drug metabolism between transgenic or gene-knockout and the parental mice.

机译：转基因或基因敲除与亲本小鼠之间参与药物代谢的酶水平的比较。

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摘要

Drug-metabolizing enzymes are involved in the metabolic activation or detoxification of carcinogens. To evaluate animals developed as models for alternative carcinogenicity testing, we investigated whether or not a gene manipulation including the transgene of ras and the knocking out of a tumor suppressor gene such as p53 or XPA could alter the expression of representative drug-metabolizing enzymes directly or indirectly. Expression of several isoforms of cytochrome P450 (CYP) in the liver of rasH2, p53 (+/-), Tg.AC, and XPA (-/-) mice with or without treatment of prototype inducer. phenobarbital or 3-methylcholanthrene, was analyzed by Western immunoblotting in comparison with their parental strains of mice. In addition, the activities of 3 major phase II enzymes, UDP-glucronosyltransferase, sulfotransferase, and glutathione S-transferase, were compared between the gene-manipulated and the corresponding parental strains of mice. Results demonstrate that XPA gene knockout appeared to increase constitutive expression of CYP2B and CYP3A isoforms. Overexpression of human c-Ha-ras gene or p53 gene knockout appeared to increase constitutive UGT activity toward 4-nitrophenol. The content or activities of almost all other enzymes examined in the present study do not appear to be affected by the gene manipulation.
机译：药物代谢酶参与致癌物的代谢活化或排毒。为了评估作为替代性致癌性测试模型而开发的动物，我们调查了包括ras转基因和敲除抑癌基因（例如p53或XPA）的基因操作是否可以直接改变代表性药物代谢酶的表达或间接地。经过或未经过原型诱导剂处理的rasH2，p53（+/-），Tg.AC和XPA（-/-）小鼠肝脏中细胞色素P450（CYP）几种同工型的表达。通过Western免疫印迹法与它们的亲本小鼠品系相比，对苯巴比妥或3-甲基胆碱进行了分析。此外，在基因操纵的小鼠和相应的亲本菌株之间比较了三种主要的II期酶的活性，即UDP-葡糖醛酸转移酶，磺基转移酶和谷胱甘肽S-转移酶。结果表明XPA基因敲除似乎增加CYP2B和CYP3A亚型的组成型表达。人c-Ha-ras基因或p53基因敲除的过表达似乎增加了组成型UGT对4-硝基苯酚的活性。本研究中检查的几乎所有其他酶的含量或活性似乎不受基因操作的影响。

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