Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.
Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.
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DOI：
10.1002/ijc.30161
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发表时间：
2016-09-01
影响因子：
6.4
通讯作者：
Wang, Xiang-Dong
中科院分区：
文献类型：
--
作者：
Aizawa, Koichi;Liu, Chun;Tang, Sanyuan;Veeramachaneni, Sudipta;Hu, Kang-Quan;Smith, Donald E.;Wang, Xiang-Dong
早期的流行病学研究报告，吸烟与肝癌有因果关系，是非酒精性脂肪性肝病(NAFLD)的独立危险因素。番茄中的番茄红素已被证明是一种潜在的预防非酒精性脂肪肝和肝细胞癌的药物。在本研究中，我们研究了烟草致癌物4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone在番茄红素干预或不干预的情况下是否会导致雪貂的肺和肝脏损伤。雄性雪貂(6组，n=8-10)分别给予NNK(50 mg/kg体重，每月1次，连续4个月)或生理盐水加或不加番茄红素(分别为2.2 mg/kg体重/天和6.6 mg/kg体重/天)，共26周。结果表明，暴露于NNK可导致雪貂肺肿瘤、肝癌和脂肪性肝炎(表现为严重的炎性细胞浸润、肝脏脂肪堆积、肝细胞气泡性变性和NF-κB表达增加)以及胆红素和天冬氨酸转氨酶水平的升高。补加两种剂量的番茄红素可抑制NNK诱导的肺组织α7烟碱型乙酰胆碱受体和肝脏NF-κB和CYP2E1mRNA的表达，减轻NNK诱导的死亡率和肺、肝的病理损害。本研究提供了强有力的实验证据，证明烟草致癌物NNK可以诱发雪貂肝细胞癌和脂肪性肝炎，为研究烟草致癌物相关的NAFLD和肝癌提供了一个有用的模型。此外，番茄红素对吸烟致癌物所致的肺和肝损伤具有潜在的保护作用。
Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury.
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影响因子：
4.2
作者：
Huang, Chin-Shiu;Liao, Jiunn-Wang;Hu, Miao-Lin
通讯作者：
Hu, Miao-Lin
DOI：
10.1158/1940-6207.capr-14-0154
发表时间：
2014-12
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Ip BC;Liu C;Ausman LM;von Lintig J;Wang XD
通讯作者：
Wang XD
DOI：
10.1016/j.lungcan.2013.09.012
发表时间：
2013-12
期刊：
Lung cancer (Amsterdam, Netherlands)
影响因子：
--
作者：
Aizawa K;Liu C;Veeramachaneni S;Hu KQ;Smith DE;Wang XD
通讯作者：
Wang XD
影响因子：
15.9
作者：
Heeschen, C;Weis, M;Cooke, JP
通讯作者：
Cooke, JP
影响因子：
5
作者：
Holick, CN;Michaud, DS;Albanes, D
通讯作者：
Albanes, D