Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers
Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers
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DOI：
10.1016/s0016-5085(99)70554-8
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发表时间：
1999-07-01
期刊：
影响因子：
29.4
通讯作者：
Watkins, PB
中科院分区：
文献类型：
--
作者：
Fontana, RJ;Lown, KS;Watkins, PB
背景与目的：炭烤肉中存在的致癌杂环胺和多环芳烃是诱导CYP1A和CYP3A酶以及p糖蛋白的底物。我们研究了碳烤肉饮食是否会导致这些蛋白质的产生。方法：健康成人10例，饲喂富含炭烤肉的日粮7 d。于第1、5、12天取十二指肠活检标本，分析CYP1A、CYP3A、p -糖蛋白信使RNA （mRNA）和蛋白。在第5天和第12天，测定肝脏CYP3A4和CYP1A2活性，并进行结肠活检。在第1、4、11和26天检测外周血单个核细胞中多环芳烃DNA加合物的水平。结果：在小肠和结肠中未检测到CYP3A4、CYP3A5或p糖蛋白mrna或蛋白的诱导，在肝脏中未检测到CYP3A4酶活性的诱导。相比之下，炭烤肉饮食导致每个受试者的肝脏和小肠中CYP1A酶的明显诱导。有;第11天外周多环芳烃DNA加合物水平与肝脏CYP1A2活性1（P = 0.027）和肠细胞CYP1A1蛋白浓度（P = 0.046）呈负相关。结论：摄入炭烤肉会诱导CYP1A酶，但不会诱导CYP3A4或p -糖蛋白。这一观察结果，结合加合物水平和CYP1A表达之间的相关性，支持CYP1A的适应性作用，而不是CYP3A4或p -糖蛋白。
Background & Aims: Carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons present in chargrilled meat are substrates for inducible CYP1A and CYP3A enzymes and for P-glycoprotein. We examined whether consumption of a chargrilled meat diet results in induction of these proteins. Methods: Ten healthy adults were fed a diet enriched with chargrilled meat for 7 days. Duodenal biopsy specimens were obtained on days 1, 5, and 12 and analyzed for CYP1A, CYP3A, and P-glycoprotein messenger RNA (mRNA) and protein. On days 5 and 12, hepatic CYP3A4 and CYP1A2 activities were measured and colon biopsies were performed. The levels of polycyclic aromatic hydrocarbon DNA adducts in peripheral blood mononuclear cells were measured on days 1, 4, 11, and 26. Results: Them was no detectable induction of CYP3A4, CYP3A5, or P-glycoprotein mRNAs or protein in small intestine or colon and no induction of hepatic CYP3A4 enzyme activity. In contrast, the chargrilled meat diet resulted in unequivocal induction of CYP1A enzymes in the liver and small intestine of each subject. There was; an inverse correlation between the level of peripheral polycyclic aromatic hydrocarbon DNA adducts measured on day 11 and both liver CYP1A2 activity 1(P = 0.027) and enterocyte CYP1A1 protein concentration (P = 0.046). Conclusions: Ingestion of chargrilled meat results in induction of CYP1A enzymes but not CYP3A4 or P-glycoprotein. This observation, combined with the correlation between adduct levels and CYP1A expression, supports an adaptive role for CYP1A but not CYP3A4 or P-glycoprotein.