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吸口甲鲶(Hypostomus affinis和Hypostomus auroguttatus,甲鲶科)肝脏中缺乏组成型和诱导型乙氧异吩恶唑酮-O-脱乙基酶活性。

Lack of constitutive and inducible ethoxyresorufin-O-deethylase activity in the liver of suckermouth armored catfish (Hypostomus affinis and Hypostomus auroguttatus, Loricariidae).

作者信息

Parente T E M, De-Oliveira A C A X, Beghini D G, Chapeaurouge D A, Perales J, Paumgartten F J R

机构信息

Laboratory of Environmental Toxicology, Department of Biological Sciences, National School of Public Health, Av Brasil 4036 (EXCAM), Rio de Janeiro, RJ 21040-361, Brazil.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2009 Aug;150(2):252-60. doi: 10.1016/j.cbpc.2009.05.006. Epub 2009 May 19.

Abstract

We investigated the presence and inducibility of CYP1A in suckermouth catfish (Hypostomus affinis and Hypostomus auroguttatus, Loricariidae), tilapia (Oreochromis niloticus, Cichlidae) and mice (Mus musculus, Muridae). Alkoxyresorufin-O-dealkylases (EROD, MROD, PROD and BROD) were detected and proved to be inducible (beta-naphthoflavone, BNF or dimethylbenz[a]anthracene, DMBA, 50 mg/kg bw ip) in liver microsomes from tilapia and mice. In loricariids, alkoxyresorufin-O-dealkylases were either undetectable (MROD/EROD) or very low (PROD/BROD), and so they remained after treatment with BNF or DMBA. Ethoxycoumarin-O-deethylase (ECOD) was recorded in all species and proved not to be inducible by BNF or DMBA. In loricariids and tilapia, ECOD was not depressed by a concentration of alpha-naphthoflavone (CYP1A-inhibitor) that markedly depressed EROD in tilapia. A CYP1A-like protein was detected by a monoclonal antibody in rats, mice and tilapia, but not in loricariids. A polyclonal antibody, however, detected a CYP1A-like protein in liver microsomes of loricariids. Suckermouth catfish, rats, mice and tilapia express a protein reactive with a polyclonal antibody against trout CYP3A. Loricariids and tilapia exhibited marked genotoxic responses (enhanced incidence of micronucleated erythrocytes) following treatment DMBA (50 mg/kg bw ip), a promutagen activated by CYP1A/1B. Therefore, although not exhibiting EROD, a CYP1A-mediated activity, loricariids converted DMBA into its genotoxic metabolites. Our findings suggest that the CYP1A-like protein of locariid catfish recognizes DMBA, but not ethoxyresorufin, as a substrate.

摘要

我们研究了吸口鲶(Hypostomus affinis和Hypostomus auroguttatus,甲鲶科)、罗非鱼(Oreochromis niloticus,丽鱼科)和小鼠(Mus musculus,鼠科)中CYP1A的存在情况及其诱导性。在罗非鱼和小鼠的肝脏微粒体中检测到了烷氧基试卤灵-O-脱烷基酶(EROD、MROD、PROD和BROD),并证明它们是可诱导的(β-萘黄酮,BNF或二甲基苯并[a]蒽,DMBA,50毫克/千克体重腹腔注射)。在甲鲶科鱼类中,烷氧基试卤灵-O-脱烷基酶要么检测不到(MROD/EROD),要么含量极低(PROD/BROD),因此在用BNF或DMBA处理后仍保持这种状态。在所有物种中都记录到了乙氧香豆素-O-脱乙基酶(ECOD),并证明其不受BNF或DMBA诱导。在甲鲶科鱼类和罗非鱼中,ECOD不会被能显著降低罗非鱼中EROD的α-萘黄酮(CYP1A抑制剂)浓度所抑制。在大鼠、小鼠和罗非鱼中,通过单克隆抗体检测到了一种CYP1A样蛋白,但在甲鲶科鱼类中未检测到。然而,一种多克隆抗体在甲鲶科鱼类的肝脏微粒体中检测到了一种CYP1A样蛋白。吸口鲶、大鼠、小鼠和罗非鱼表达一种与抗鳟鱼CYP3A多克隆抗体发生反应的蛋白。在用CYP1A/1B激活的前诱变剂DMBA(50毫克/千克体重腹腔注射)处理后,甲鲶科鱼类和罗非鱼表现出明显的遗传毒性反应(微核红细胞发生率增加)。因此,尽管甲鲶科鱼类不表现出EROD这种CYP1A介导的活性,但它们能将DMBA转化为其遗传毒性代谢产物。我们的研究结果表明,甲鲶科鲶鱼的CYP1A样蛋白将DMBA识别为底物,但不将乙氧基试卤灵识别为底物。

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