In vitro studies of the influence of glutathione transferases and epoxide hydrolase on the detoxification of acrylamide and glycidamide in blood
In vitro studies of the influence of glutathione transferases and epoxide hydrolase on the detoxification of acrylamide and glycidamide in blood
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DOI：
10.1016/j.mrgentox.2004.11.006
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发表时间：
2005-02-07
影响因子：
1.9
通讯作者：
Warholm, M
中科院分区：
文献类型：
--
作者：
Paulsson, B;Rannug, A;Warholm, M
参与外源物质代谢的酶在人体内通常是多态的。这种遗传多态性可能导致某些化学品解毒方面的个体间差异，从而可能影响健康风险评估。本文研究了多态酶对丙烯酰胺及其代谢物丙烯酰胺解毒的影响。促进与谷胱甘肽（GSH）结合的酶，即谷胱甘肽转移酶（GSTs），可能影响丙烯酰胺和glycidamide的解毒，而环氧化物水解酶（EH）只能催化glycidamide的水解。在这项研究中，丙烯酰胺或甘油酰胺作为血红蛋白（Hb）的特定加合物在体外培养后的血液样本中进行剂量分析。研究了GSTT1和GSTM1不同基因型个体的血样。不同基因型的加合物水平无显著差异。在平行实验中，用环氧乙烷孵育作为阳性对照。在本实验中，携带GSTT1的个体比缺乏GSTT1的个体表现出较低的环氧乙烷加合物水平增量。此外，分别抑制GST和EH的乙酸或十二胺的添加对加合物水平没有影响。这些结果表明，在暴露于丙烯酰胺或丙烯酰胺后，GSTs和EH对血液剂量（以hb加合物随时间测量）都没有任何显著影响。(C) 2004 Elsevier B.V.版权所有
Enzymes involved in the metabolism of xenobiotic substances are often polymorphic in humans. Such genetic polymorphisms may result in inter-individual differences in detoxification of certain chemicals, and as a consequence, possibly affect health-risk assessments. This present work concerns studies of the influence of polymorphic enzymes in the detoxification of acrylamide and its metabolite glycidamide. Enzymes that enhance conjugation with glutathione (GSH), the glutathione transferases (GSTs), may influence the detoxification of both acrylamide and glycidamide, whereas the enzyme epoxide hydrolase (EH) should only catalyse the hydrolysis of glycidamide. In this study, the doses of acrylamide or glycidamide measured as specific adducts to hemoglobin (Hb) were analysed in blood samples after in vitro incubation with these compounds. Blood samples from individuals with different genotypes for GSTT1 and GSTM1 were studied. No significant differences in adduct levels depending on genotype were noted. In a parallel experiment, incubation with ethylene oxide was used as positive control. In this experiment individuals carrying GSTT1 showed lower adduct level increments from ethylene oxide than individuals lacking GSTT1. Furthermore, addition of ethacrynic acid or laurylamine, compounds which inhibit GST and EH, respectively, did not affect the adduct levels. These results suggest that neither GSTs nor EH have any significant effect on the blood dose, measured as Hb-adducts over time, after exposure to acrylamide or glycidamide. (C) 2004 Elsevier B.V. All rights reserved.