Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers:: Role of glutathione S-transferase genotypes
Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers:: Role of glutathione S-transferase genotypes
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DOI：
10.1158/1055-9965.epi-03-0193
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发表时间：
2004-02-01
影响因子：
3.8
通讯作者：
Ali, IU
中科院分区：
文献类型：
--
作者：
Hakim, IA;Harris, RB;Ali, IU
谷胱甘肽S-转移酶（GST）是异生物质代谢的第二阶段酶，已在表型和基因型水平上得到了广泛的研究。GST mu 1（GSTM 1）和GST theta 1（GSTT 1）基因具有空等位基因变体，其中整个基因缺失。这两种酶的无效基因型与许多不同类型的肿瘤有关。本研究的目的是确定GSTM 1和GSTT 1基因型对吸烟的氧化应激敏感性增加的可能差异，以及高饮茶对此的影响。我们设计了一项II期随机、对照、三臂茶干预试验，以研究在重度吸烟者中，通过尿8-羟基脱氧鸟苷（8-OHdG）测定，在4个月的时间内大量饮用（4杯/天）脱咖啡因的绿色或红茶或水对氧化DNA损伤的影响，并评估GSTM 1和GSTT 1基因型作为效应修饰剂的作用。共有133名重度吸烟者（100名女性和33名男性）完成了干预。GSTM 1和GSTT 1基因型状态用基于PCR的方法确定。使用多元线性回归模型估计绿色茶和红茶消费对肌酐校正的尿8-OHdG的主效应和相互作用效应，调整或不调整潜在的混杂因素。最后，我们研究了GSTM 1和绿色茶的治疗效果是否会在4个月后降低尿中8-OHdG水平。校正基线测量值和其他潜在混杂因素后，对尿8-OHdG的评估显示，饮用绿色茶对尿8-OHdG有显著影响（P = 0.001）。GSTM 1阳性（t = -2.99; P = 0.006）和GSTT 1阳性（P = 0.004）绿色茶组较基线的变化显著，但GSTM 1阴性（P = 0.07）或GSTT 1阴性（P = 0.909）绿色茶组无显著变化。饮用脱咖啡因红茶对重度吸烟者的尿8-OHdG水平没有影响。我们的数据表明，每天饮用4杯茶是一种可行且安全的方法，并且与绿色茶消费者在饮用4个月后尿中8-OHdG的显着减少有关。这一发现也表明，绿色茶干预可能是有效的亚组吸烟者谁是GSTM 1和/或GSTT 1阳性。
Glutathione S-transferase (GST), a member of the phase II group of xenobiotic metabolizing enzymes, has been intensively studied at the levels of phenotype and genotype. The GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null-allele variant in which the entire gene is absent. The null genotype for both enzymes has been associated with many different types of tumors. The aim of this study was to determine the possible differences in increased oxidative stress susceptibility to smoking within the GSTM1 and GSTT1 genotypes and the impact of high tea drinking on this. We designed a Phase II randomized, controlled, three-arm tea intervention trial to study the effect of high consumption (4 cups/day) of decaffeinated green or black tea, or water on oxidative DNA damage, as measured by urinary 8-hydroxydeoxyguanosine (8-OHdG), among heavy smokers over a 4-month period and to evaluate the roles of GSTM1 and GSTT1 genotypes as effect modifiers. A total of 133 heavy smokers (100 females and 33 males) completed the intervention. GSTM1 and GSTT1 genotype statuses were determined with a PCR-based approach. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Finally, we studied whether the effect of treatment varied by GSTM1 and green tea showed a decrease in urinary 8-OHdG levels after 4 months. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed significant effect for green tea consumption (P = 0.001). The change from baseline was significant in both GSTM1-positive (t = -2.99; P = 0.006) and GSTT1-positive (P = 0.004) green tea groups, but not in the GSTM1-negative (P = 0.07) or GSTT1-negative (P = 0.909) green tea groups. Decaffeinated black tea consumption had no effect on urinary 8-OHdG levels among heavy smokers. Our data show that consumption of 4 cups of tea/day is a feasible and safe approach and is associated with a significant decrease in urinary 8-OHdG among green tea consumers after 4 months of consumption. This finding also suggests that green tea intervention may be effective in the subgroup of smokers who are GSTM1 and/or GSTT1 positive.