Effect of chronic dietary ethanol in the promotion of N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats


Dr Mikihiro Tsutsumi, Division of Gastroenterology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. Email: tsutsumi@kanazawa-med.ac.jp


Background:  The pathogenetic correlation between chronic alcohol consumption and development of esophageal cancer is not clear. The role of alcohol abuse in the carcinogenic action of N-nitrosomethylbenzylamine, which induces tumors in the esophagus, has been evaluated.

Methods:  Twenty male rats were fed liquid diets containing ethanol or carbohydrates for 30 weeks. N-nitrosomethylbenzylamine (0.1 mg/kg, twice a week) was injected i.p. from the 9th to 19th week. The pair feeding was stopped at 9.00 am and N-nitrosomethylbenzylamine was administered at 10.00 am. Ethanol was not detected in the blood at the time of injection. Liquid diets were provided again at 3 pm until 9 am next day. The animals were killed at the end of the 30th week. The esophagi were collected and examined for visible tumors. The tissue sections were stained for histology and CYP2E1expression.

Results:  While 5–8 esophageal squamous polyps developed in all rats in the ethanol group, only one polyp each was formed in five out of the 10 rats in the control group. The size of the polyps was significantly larger in the ethanol group, when compared to the control group. Invasive squamous cell carcinoma was also observed in 50% of the animals in the ethanol group. Cytochrome P4502E1 (CYP2E1) staining demonstrated marked expression in the esophageal mucosa in the ethanol group, but not in the control group.

Conclusions:  The increased expression of CYP2E1 induced by chronic ethanol consumption promotes the development of N-nitrosomethylbenzylamine-induced esophageal tumorigenesis. However, the molecular mechanism of the increased production of esophageal tumors during alternative administration of N-nitrosomethylbenzylamine and ethanol is not clear.