Concentration dependent effects of tobacco particulates from different types of cigarettes on expression of drug metabolizing proteins, and benzo(a)pyrene metabolism in primary normal human oral epithelial cells.

Concentration dependent effects of tobacco particulates from different types of cigarettes on expression of drug metabolizing proteins, and benzo(a)pyrene metabolism in primary normal human oral epithelial cells.
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来自不同类型的香烟的烟草颗粒物对药物代谢蛋白表达的浓度依赖性作用,以及原发性正常人口腔上皮细胞中苯并(A)pyrene代谢的浓度。

DOI:
10.1016/j.fct.2011.06.037
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发表时间:
2011-09
影响因子:
4.3
通讯作者:
Guttenplan, Joseph B.
Guttenplan, Joseph B.
中科院分区:
农林科学2区
文献类型:
--
作者:
Sacks, Peter G.;Zhao, Zhong-Lin;Kosinska, Wieslawa;Fleisher, Kenneth E.;Gordon, Terry;Guttenplan, Joseph B.

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烟草烟雾(TS)调节I、II相酶和影响烟草致癌物代谢的能力可能是其致癌性的重要因素。首次比较了几种类型的TS微粒(TSP)在不同的原代培养的人口腔上皮细胞(NOE)中影响烟草致癌物(BaP)代谢为遗传毒性产物和药物代谢酶表达的能力。测试了来自参考过滤(2RF4)、薄荷(MS)、参考未过滤(IR3)、超低焦油(UL)和主要加热烟草(ECL)的香烟的TSP。用0.2 - 10 µ g/ml TSP浓度预处理的细胞通常显示BaP代谢速率增加;用高于10 µ g/ml TSP浓度处理的细胞显示速率降低。当以重量为基础表示时,TSP的效果相似。TSP/烟重的变化顺序为MS/IR 3> 2RF 4> ECL> UL。通过qRT-PCR评估,所有TSP均诱导I相蛋白、细胞色素P450 1A1(CYP1A1)和1B1(CYP1B1)、II相蛋白、NAD(P)H脱氢酶醌1(NQO1)和微粒体谷胱甘肽S-转移酶1(MGST 1)以及羟基类固醇(17-β)脱氢酶2(HSD17 B2)。在可能的生理水平上,基因诱导的模式有利于激活而不是解毒。
The ability of tobacco smoke (TS) to modulate phase I and II enzymes and affect metabolism of tobacco carcinogens is likely an important factor in its carcinogenicity. For the first time several types of TS particulates (TSP) were compared in different primary cultured human oral epithelial cells (NOE) for their abilities to affect metabolism of the tobacco carcinogen, (BaP) to genotoxic products, and expression of drug metabolizing enzymes. TSP from, reference filtered (2RF4), mentholated (MS), reference unfiltered, (IR3), ultra low tar (UL), and cigarettes that primarily heat tobacco (ECL) were tested. Cells pretreated with TSP concentrations of 0.2 – 10 µg/ml generally showed increased rates of BaP metabolism; those treated with TSP concentrations above 10 µg/ml showed decreased rates. Effects of TSPs were similar when expressed on a weight basis. Weights of TSP/cigarette varied in the order: MS ≈ IR3 > 2RF4 > ECL > UL. All TSPs induced the phase I proteins, cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1), phase II proteins, NAD(P)H dehydrogenase quinone 1 (NQO1), and microsomal glutathione S-transferase 1 (MGST1), and additionally, hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2), as assessed by qRT-PCR. The pattern of gene induction at probable physiological levels favored activation over detoxification.
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发表时间: 2005-07-01
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