Dusinská M, Ficek A, Horská A, Raslová K, Petrovská H, Vallová B, Drlicková M, Wood S G, Stupáková A, Gasparovic J, Bobek P, Nagyová A, Kováciková Z, Blazícek P, Liegebel U, Collins A R
Department of Molecular and Genetic Toxicology, Institute of Preventive and Clinical Medicine, Limbova 14, 83301 Bratislava, Slovak Republic.
Mutat Res. 2001 Oct 1;482(1-2):47-55. doi: 10.1016/s0027-5107(01)00209-3.
Glutathione S-transferase genotypes GSTT1, GSTM1, GSTP1 were characterised in 155 middle-aged men and compared with parameters of oxidative stress at the level of DNA and lipids, with antioxidant enzymes, and with plasma antioxidants in smokers and non-smokers. Smokers had on average significantly lower levels of Vitamin C, beta-carotene and beta-cryptoxanthin and higher amounts of oxidised purines and pyrimidines in lymphocyte DNA. The GSTM1 null genotype was associated with elevated glutathione as well as with higher Vitamin C concentration in plasma. Vitamin C was higher in GSTT1+ compared with GSTT1 null--as was glucose-6-phosphate dehydrogenase activity. The homozygous GSTP1 a/a genotype was associated with significantly higher levels of GST activity measured in lymphocytes, in comparison with the b/b genotype. Using multifactorial statistical analysis we found significant associations between smoking, GSTP1 genotype, plasma Vitamin C, and purine base damage in lymphocyte DNA. The difference in Vitamin C plasma levels between smokers and non-smokers was seen only with the GSTP1 b/b genotype. This group accounted also for most of the increase in purine oxidation in smokers. In contrast, the link between smoking and oxidised pyrimidines in DNA was seen only in the GSTT1 null group. It seems that polymorphisms in the phase II metabolising enzyme glutathione S-transferase may be important determinants of commonly measured biomarkers.
对155名中年男性的谷胱甘肽S-转移酶基因型GSTT1、GSTM1、GSTP1进行了特征分析，并与吸烟者和非吸烟者在DNA和脂质水平上的氧化应激参数、抗氧化酶以及血浆抗氧化剂进行了比较。吸烟者的维生素C、β-胡萝卜素和β-隐黄质平均水平显著较低，淋巴细胞DNA中的氧化嘌呤和嘧啶含量较高。GSTM1无效基因型与血浆中谷胱甘肽升高以及维生素C浓度升高有关。与GSTT1无效基因型相比，GSTT1阳性基因型的维生素C水平更高，葡萄糖-6-磷酸脱氢酶活性也是如此。与b/b基因型相比，纯合GSTP1 a/a基因型与淋巴细胞中测得的GST活性显著较高有关。使用多因素统计分析，我们发现吸烟、GSTP1基因型、血浆维生素C和淋巴细胞DNA中的嘌呤碱基损伤之间存在显著关联。吸烟者和非吸烟者之间血浆维生素C水平的差异仅在GSTP1 b/b基因型中可见。该组也占吸烟者嘌呤氧化增加的大部分。相比之下，吸烟与DNA中氧化嘧啶之间的联系仅在GSTT1无效组中可见。看来II期代谢酶谷胱甘肽S-转移酶的多态性可能是常用生物标志物的重要决定因素。
