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Modulation of the GSTT1 activity by the GSTM1 phenotype in a sample of Italian farm-workers

机译:意大利农场工人样本中GSTM1表型对GSTT1活性的调节

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Glutathione S-transferase (GST) isozymes catalyze nucleophilic attack by reduced Glutathione (GSH) on a variety of electrophilic compounds and play a central role in biotransformation of xenobiotics (Hayes et al., Annu Rev Pharmacol Toxicol 45:51–88, 2005). We performed a case–control study to evaluate the GSTM1 and GSTT1 polymorphisms and to investigate if exposure to pesticides conditions the GSTT1 activity level in 115 healthy controls and 90 farm-workers exposed to pesticides. Polymorphisms were investigated using a GSTM1 or a GSTT1-specific PCR. Enzyme activity was measured by means of DCM as co-substrate, as described by Bruhn et al. (Biochem Pharmacol 56:1189–1193, 1998). There was no significant difference between the farm-workers and the healthy controls regarding the distribution of various alleles of the GSTM1 and GSTT1 genes and the GSTT1 enzyme activity. In farm-workers, the GSTM1 null genotype was associated with a significant increase of GSTT1 activity, suggesting a regulative mechanism common to GSTM1 and GSTT1 enzymes after exposure to xenobiotics.
机译:谷胱甘肽S-转移酶(GST)同工酶通过还原型谷胱甘肽(GSH)对多种亲电子化合物催化亲核攻击,并在异源生物的生物转化中发挥重要作用(Hayes等人,Annu Rev Pharmacol Toxicol 45:51–88,2005)。 。我们进行了一项病例对照研究,以评估GSTM1和GSTT1多态性,并调查是否接触农药限制了115名健康对照和90名暴露于农药的农场工人的GSTT1活性水平。使用GSTM1或GSTT1特异性PCR研究了多态性。如Bruhn等人所述,酶活性是通过DCM作为共底物来测量的。 (Biochem Pharmacol 56:1189-1119,1998)。在农场工人和健康对照者之间,关于GSTM1和GSTT1基因的各种等位基因的分布以及GSTT1酶的活性没有显着差异。在农场工人中,GSTM1无效基因型与GSTT1活性的显着增加有关,这表明暴露于异源生物后GSTM1和GSTT1酶共有的调节机制。

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