Metabolism of isothiocyanates in individuals with positive and null GSTT1 and M1 genotypes after drinking watercress juice
Metabolism of isothiocyanates in individuals with positive and null GSTT1 and M1 genotypes after drinking watercress juice
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DOI：
10.1016/j.clnu.2010.06.010
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发表时间：
2010-12-01
影响因子：
6.3
通讯作者：
Chung, Fung-Lung
中科院分区：
文献类型：
--
作者：
Dyba, Marcin;Wang, Antai;Chung, Fung-Lung
背景与目的：从十字花科蔬菜中提取的异硫氰酸酯（ITCs）在人类细胞培养、动物模型和流行病学研究中已被证明是有前景的抗癌药物。几项流行病学研究表明，饮食中摄入异硫氰酸酯与患癌症，特别是肺癌、结肠癌和乳腺癌的风险呈负相关。更重要的是，膳食中ITCs的保护作用似乎受到谷胱甘肽s -转移酶（GST）基因型的影响；其中，谷胱甘肽s -转移酶theta 1 （GSTT1）和谷胱甘肽s -转移酶Mu 1 （GSTM1）为零的个体比GSTT1和M1阳性的个体受到更好的保护。尽管大多数研究，特别是那些在接触ITC丰富饮食的人群中进行的研究，证明了这种影响，但也有一些研究表明相反或没有关联。虽然饮食中的ITCs与GST基因相互作用的证据相对较强，但造成差异效应的原因尚不清楚。在这项研究中，我们研究了一种可能的机制：在饮用富含ITCs的豆菜汁后，基因型为零的受试者是否比基因型为阳性的受试者分泌ITCs的速度慢。方法：共纳入48例受试者，其中GSTT1和M1阳性28例，阴性基因型20例。在饮用豆瓣菜汁后24小时内收集5份尿液样本来确定排泄率。结果：阳性和阴性基因型两组异硫氰酸酯排泄率和排泄高峰时间差异无统计学意义。结论：GSTT1和M1基因型不太可能与豆瓣菜中ITCs的排泄率有关。具有两种基因型的受试者之间所显示的保护差异不太可能是由于总体ITC排泄率的差异，然而，需要调查除PEITC之外的ITC排泄率。其他尚未确定的机制可能是膳食中ITCs和GST基因型之间的饮食和基因相互作用在人类癌症预防中的基础。需要进一步的研究来评估异硫氰酸酯抗癌的保护机制。(C) 2010爱思唯尔有限公司和欧洲临床营养与代谢学会。版权所有。
Background & aims: Isothiocyanates (ITCs) derived from cruciferous vegetables have been shown to be promising agents against cancer in human cell culture, animal models, and in epidemiological studies. Several epidemiological studies have demonstrated an inverse relationship between intake of dietary isothiocyanates and the risk of cancers, particularly lung, colon, and breast. More importantly, the protective effects of dietary ITCs appear to be influenced by glutathione S-transferase (GST) genotype; specifically, individuals with glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase Mu 1 (GSTM1) null are better protected than those with GSTT1 and M1 positive. Although the majority of studies, especially those conducted in populations exposed to ITC rich diets, demonstrated such effects, there are a few studies that showed opposite or no association. While evidence for the interactions of dietary ITCs with GST genes is relatively strong, the reasons for the differential effects remain unclear. In this study, we examined one possible mechanism: whether subjects with null genotypes excrete ITCs at a slower rate than those with positive genotypes after drinking watercress juice, a rich source of ITCs.Methods: A total of 48 subjects, 28 GSTT1 and M1 positive and 20 null genotypes were enrolled in the study. The rates of excretion were determined using five urine samples collected over a period of 24 h after drinking watercress juice.Results: No statistically significant differences in the rates of isothiocyanate excretion and the time of peak excretion were observed between the two tested groups having positive and null genotypes.Conclusions: GSTT1 and M1 genotypes are not likely to be involved in the rate of excretion of ITCs in watercress. The demonstrated differences in protection among subjects with the two genotypes are not likely due to differences in overall ITC excretion rates, however, excretion rates of ITCs other than PEITC need to be investigated. Other yet to be identified mechanism(s) may underlie the diet and gene interactions between dietary ITCs and GST genotypes in human cancer prevention. Further research is needed to evaluate the protective mechanisms of isothiocyanates against cancer. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.