Premium
Tobacco carcinogen induces both lung cancer and non‐alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation
Author(s) -
Aizawa Koichi,
Liu Chun,
Tang Sanyuan,
Veeramachaneni Sudipta,
Hu KangQuan,
Smith Donald E.,
Wang XiangDong
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30161
Subject(s) - steatohepatitis , hepatocellular carcinoma , medicine , lycopene , carcinogen , lung cancer , liver cancer , fatty liver , pathology , steatosis , endocrinology , gastroenterology , biology , carotenoid , botany , genetics , disease
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.