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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). 4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁酮(NNK)。
Pub Date : 2011-04-15 DOI: 10.1158/1538-7445.AM2011-3236
Xinxin Ding, Xin Zhou
Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLNNK is a potent lung procarcinogen. Previously, we have demonstrated that NNK-induced lung tumorigenesis depends on target-tissue metabolic activation by pulmonary P450 enzymes. The aim of this study is to test the hypotheses that 1) mouse CYP2A5 plays an essential role in NNK bioactivation in the lung, and 2) transgenic expression of human CYP2A13, known to be selectively expressed in the respiratory tract, and be the most efficient enzyme for NNK metabolic activation in vitro, can increase the rates of NNK metabolic activation in the mouse lung. We determined the rates of in vitro formation of 4-oxo-4-(3-pyridyl)-butanal (OPB), representing the reactive intermediate that can lead to the further formation of O6-mehtylguanine (O6-mG) DNA adduct, in liver and lung microsomes of wild-type, Cyp2a5-null, and CYP2A13-humanized (CYP2A13-transgenic/Cyp2a5-null) mice. We found that, in both liver and lung microsomes, the loss of CYP2A5 resulted in significant decreases in the rates of formation of OPB; whereas, the gain of CYP2A13 led to recovery of the microsomal activity in the lung, but not in the liver. Furthermore, we observed that the levels of O6-mG, the DNA adduct known to be most highly correlated with incidences of lung tumor formation, were significantly higher in the lungs of the CYP2A13-humanized mice, than in the Cyp2a5-null mice. In control experiments, rates of systemic clearance of NNK and its major circulating metabolite, NNAL, were confirmed to be not different among the three mouse strains. These results indicate that CYP2A13 can catalyze NNK bioactivation in vivo, and they support the idea that CYP2A13 genetic polymorphisms can influence the risks of tobacco-induced lung tumorigenesis in humans. (Supported in part by NIH grant CA092596)Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3236. doi:10.1158/1538-7445.AM2011-3236
会议记录:AACR第102届年会2011年4月2日至6日;奥兰多,FLNNK是一种强效的肺前致癌物。之前,我们已经证明nnk诱导的肺肿瘤发生依赖于肺P450酶的靶组织代谢激活。本研究的目的是验证以下假设:1)小鼠CYP2A5在肺内NNK的生物激活中起着至关重要的作用;2)人类CYP2A13转基因表达可以提高小鼠肺内NNK的代谢激活率。已知CYP2A13在呼吸道中选择性表达,是体外最有效的NNK代谢激活酶。我们测定了在野生型、cyp2a13缺失型和cyp2a13人源化(cyp2a13转基因/ cyp2a5缺失型)小鼠的肝脏和肺微粒体中,4-氧-4-(3-吡啶基)-丁醛(OPB)的体外形成率,OPB是一种活性中间体,可导致o6 -甲基鸟嘌呤(O6-mG) DNA加合物的进一步形成。我们发现,在肝脏和肺微粒体中,CYP2A5的缺失导致OPB形成率显著降低;然而,CYP2A13的增加导致肺微粒体活性的恢复,但在肝脏中没有。此外,我们观察到,在cyp2a13人源化小鼠的肺中,O6-mG(已知与肺肿瘤形成发生率高度相关的DNA加合物)的水平显著高于cyp2a5缺失小鼠。在对照实验中,证实了三种小鼠品系对NNK及其主要循环代谢物NNAL的全身清除率没有差异。这些结果表明CYP2A13可以在体内催化NNK的生物活化,支持CYP2A13基因多态性可以影响烟草诱导的人类肺肿瘤发生风险的观点。(部分由NIH拨款CA092596支持)引用格式:{Authors}。【摘要】。摘自:美国癌症研究协会第102届年会论文集;2011年4月2-6日;费城(PA): AACR;癌症杂志,2011;71(8增刊):摘要第3236期。doi: 10.1158 / 1538 - 7445. - am2011 - 3236
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引用次数: 23
Sample Preparation Techniques for Environmental Organic Pollutant Analysis 环境有机污染物分析的样品制备技术
Pub Date : 2011-03-16 DOI: 10.1002/9780813823621.CH14
R. Clement, C. Hao
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引用次数: 0
Benzo[ghi]perylene. 苯佐(ghi] perylene。
Pub Date : 2007-04-18 DOI: 10.1201/9781420009132-38
J. Montgomery
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引用次数: 3
Benzo[k]fluoranthene. 苯并[k]荧蒽。
Pub Date : 2007-04-18 DOI: 10.1201/9781420009132-36
John Montgomery
A pale yellow aromatic hydrocarbon consisting of five fused rings and is produced by the incomplete combustion of organic matter. Benzo(k)fluoranthene is primarily found in gasoline exhaust, cigarette smoke, coal tar, coal and oil combustion emissions, lubricating oils, used motor oils and crude oils. T his substance is used only for research purposes. Benzo(k)fluoranthene is reasonably anticipated to be a human carcinogen. (NCI05) Qeios · Definition, February 7, 2020
一种淡黄色的芳香烃,由五个熔合环组成,由有机物不完全燃烧产生。苯并(k)氟蒽主要存在于汽油废气、香烟烟雾、煤焦油、煤和石油燃烧排放物、润滑油、二手机油和原油中。这种物质仅用于研究目的。苯并(k)氟蒽被合理地预测为人类致癌物。(NCI05) Qeios·定义,2020年2月7日
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引用次数: 7
Indeno [1,2,3-cd]pyrene. 茚并[1,2,-cd]芘。
Pub Date : 2007-04-18 DOI: 10.1002/9780470114735.hawley08876
J. Montgomery
A yellowish, aromatic hydrocarbon consisting of six fused rings and produced by the incomplete combustion of organic matter. Indene[1,2,3-cd]pyrene is primarily found in certain foods, gasoline and diesel exhaust, cigarette smoke, coal tar and coal tar pitch, soot and petroleum asphalt. T his substance is used only for research purposes. Indene[1,2,3-cd]pyrene is reasonably anticipated to be a human carcinogen. (NCI05) Qeios · Definition, February 7, 2020
芳烃一种淡黄色的芳烃,由六个熔合环组成,由有机物不完全燃烧产生茚[1,2,3-cd]芘主要存在于某些食品、汽油和柴油废气、香烟烟雾、煤焦油和煤焦油沥青、煤烟和石油沥青中。这种物质仅用于研究目的。茚[1,2,3-cd]芘被合理地认为是一种人类致癌物。(NCI05) Qeios·定义,2020年2月7日
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引用次数: 6
Attapulgite. 凹凸棒石。
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引用次数: 0
Sepiolite. 海泡石。
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引用次数: 0
Silica and some silicates. 二氧化硅和一些硅酸盐。
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引用次数: 0
Erionite. Erionite。
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引用次数: 0
Wollastonite. 硅灰石。
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引用次数: 0
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IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans
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