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首页> 外文期刊>Archives of Toxicology >Inhalation of toluene diisocyanate affects cytochrome P450 2B1 expression in rat lung.
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Inhalation of toluene diisocyanate affects cytochrome P450 2B1 expression in rat lung.

机译：吸入甲苯二异氰酸酯会影响大鼠肺中细胞色素P450 2B1的表达。

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In the lung the expression of xenobiotic-metabolizing enzymes such as cytochromes P450 (CYP) and glutathione S-transferases (GST) may be affected by inhaled pollutants. Toluene diisocyanate (TDI) is a highly volatile chemical compound known to induce a wide array of diseases in workers exposed to vapors or sprays, including respiratory allergy and asthma. We investigated the effect of inhaled TDI on expression of CYP 1A1, 2B1, 2E1, and 3A1 and of alpha-, mu-, and pi-GST in rat lung. Animals were exposed to targeted concentrations of 0.01, 0.1, or 1 ppm TDI vapors or to cleaned filtered air for 8 h. Expression of CYP and GST was analyzed 18 24 h after the end of exposure using western blotting, northern blotting, and immunohistochemistry. Constitutive levels of CYP 2B1 and 3A1 proteins were found in lung tissue from control rats, whereas CYP 1A1 and 2E1 proteins were not detectable. Animal exposure to TDI vapors neither modified CYP 3A1 protein expression, nor led to any detectable expression of CYP 1A1 or 2E1. In contrast, exposure to 1 ppm TDI induced a 40% reduction in CYP 2B1 protein levels. This decrease was associated with a 33% decrease in CYP 2B1 mRNA levels. Additionally, CYP 2B1 immunolabeling localized to ciliated epithelial cells, Clara cells, and type II alveolar cells in the lung tissue of control rats was markedly decreased in animals exposed to 1 ppm TDI. Constitutive levels of alpha-, mu-, and pi-GST proteins were found in lung tissue from control rats. Exposure to TDI had no effect on lung expression of either of the GST. In conclusion, this study clearly shows a selective decrease in CYP 2B1 expression by TDI vapors in rat lung. The contribution of CYP 2B1 to metabolize further xenobiotics is therefore altered.
机译：在肺中，吸入污染物会影响异种代谢酶（例如细胞色素P450（CYP）和谷胱甘肽S-转移酶（GST））的表达。甲苯二异氰酸酯（TDI）是一种高挥发性化合物，已知会在暴露于蒸气或喷雾的工人中诱发多种疾病，包括呼吸道过敏和哮喘。我们调查了吸入TDI对大鼠肺中CYP 1A1、2B1、2E1和3A1以及α-，mu-和pi-GST表达的影响。将动物暴露于0.01、0.1或1 ppm TDI蒸气的目标浓度下，或暴露于清洁的过滤空气中8小时。暴露结束后18 24 h，使用western blotting，northern blotting和免疫组化分析CYP和GST的表达。在对照组大鼠的肺组织中发现了CYP 2B1和3A1蛋白的组成水平，而未检测到CYP 1A1和2E1蛋白。动物在TDI蒸气中的暴露既不会改变CYP 3A1蛋白的表达，也不会导致任何可检测到的CYP 1A1或2E1的表达。相反，暴露于1 ppm TDI会引起CYP 2B1蛋白水平降低40％。这种降低与CYP 2B1 mRNA水平降低33％有关。此外，在暴露于1 ppm TDI的动物中，CYP 2B1免疫标记局限于对照组大鼠肺组织中的纤毛上皮细胞，Clara细胞和II型肺泡细胞。在对照大鼠的肺组织中发现了α-，mu-和pi-GST蛋白的组成水平。暴露于TDI对任何一种GST的肺表达均无影响。总之，这项研究清楚地表明，TDI蒸气在大鼠肺中选择性降低了CYP 2B1表达。 CYP 2B1代谢其他异生素的贡献因此改变。

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