Pilot study of free and conjugated urinary mutagenicity during consumption of pan-fried meats: possible modulation by cruciferous vegetables, glutathione S-transferase-M1, and N-acetyltransferase-2

Pilot study of free and conjugated urinary mutagenicity during consumption of pan-fried meats: possible modulation by cruciferous vegetables, glutathione S-transferase-M1, and N-acetyltransferase-2
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DOI:
10.1016/s0027-5107(97)00152-8
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发表时间:
1997-11-19
影响因子:
2.3
通讯作者:
Kohlmeier, L
Kohlmeier, L
中科院分区:
医学4区
文献类型:
--
作者:
DeMarini, DM;Hastings, SB;Kohlmeier, L

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流行病学和实验证据表明,与某些I期和II期代谢基因型一起食用油炸肉类会增加患结直肠癌的风险。与此同时,食用十字花科蔬菜可以降低患结肠癌的风险。因此,我们设计了一项为期6周的先导喂养研究,以评估这些变量对尿致突变性的影响,尿致突变性是与油炸肉类消费相关的生物标志物。八名受试者连续六周每天吃油炸肉;以过量产生乙酰转移酶的移码菌株YG1024为研究对象,研究了S9的存在对尿致突变性的影响。每周一次采集24小时尿液的C18/甲醇提取物进行未水解(游离诱变性)和水解(总诱变性)试验;两者的不同之处在于共轭诱变性。虽然不显著,但在食用十字花科植物的人群中,偶联尿致突变性水平翻了一番,而在食用非十字花科植物的人群中,偶联尿致突变性水平下降到初始水平的30%,这表明十字花科植物可能会提高食用油炸肉类导致的偶联尿致突变性水平。这种效应与文献记载的十字花科蔬菜诱导II期酶的能力是一致的。与NAT2慢速受试者相比,NAT2快速表型与偶联性(p = 0.05)和总尿致突变性(p = 0.004)增加近2倍显著相关,这与NAT2快速表型证实的肉类消费者患结直肠癌的风险升高一致。与GSTM1(+)受试者相比,GSTMI(-)受试者的尿致突变性增加了2倍,在自由尿致突变性(p = 0.18)和总尿致突变性(p = 0.13)方面接近显著性。这是关于(a)水解尿液致突变性的第一份报告,水解尿液的致突变性始终比未水解尿液更强;(b)十字花科植物可能增强偶联尿致突变性;(c)快速NAT2和可能的GSTM1(-)表型与油炸肉相关尿致突变性水平升高的关系。(C) 1997爱思唯尔科学有限公司
Epidemiological and experimental evidence indicates that consumption of fried meats in conjunction with certain genotypes of phase I and II metabolism genes poses an elevated risk for colorectal cancer. Parallel to this, the consumption of cruciferous vegetables is associated with a reduced risk of colon cancer. Therefore, we designed a 6-week pilot feeding study to evaluate the effect of these variables on urinary mutagenicity, which is a biomarker associated with fried-meat consumption. Eight subjects were fed fried meats daily for six weeks; four ate cruciferous vegetables, and four ate non-cruciferous vegetables, Urinary mutagenicity was evaluated in the presence of S9 in strain YG1024 of Salmonella, which is a frameshift strain that overproduces acetyltransferase. C18/methanol extracts of 24-h urines collected once each week were tested unhydrolyzed (free mutagenicity) and hydrolyzed (total mutagenicity); the difference between the two was the conjugated mutagenicity. Although not significant, the levels of conjugated urinary mutagenicity doubled among crucifera consumers and decreased to 30% of the initial levels among non-crucifera consumers, suggesting the possibility that crucifera may enhance the level of conjugated urinary mutagenicity resulting from consumption of fried meats. Such an effect would be consistent with the documented ability of cruciferous vegetables to induce phase II enzymes. The NAT2 rapid phenotype was significantly associated with similar to 2-fold increases in conjugated(p = 0.05) and total (p = 0.004) urinary mutagenicity relative to NAT2 slow subjects, consistent with the elevated risk confirmed by the NAT2 rapid phenotype for colorectal cancer among meat consumers, An similar to 2-fold increase in urinary mutagenicity among the GSTMI(-) subjects relative to the GSTM1(+) subjects approached significance for free (p = 0.18) and total (p = 0.13) urinary mutagenicity. This is the first report on (a) the mutagenicity of hydrolyzed urine, which was consistently more mutagenic than unhydrolyzed urine; (b) the potential enhancement of conjugated urinary mutagenicity by crucifera; and (c) the association of the rapid NAT2 and possibly the GSTM1(-) phenotype with elevated levels of fried meat-associated urinary mutagenicity. (C) 1997 Elsevier Science B.V.