Enhancing effect of ethanol on esophageal tumor development in rats by initiation of diethylnitrosamine

The effects of ethanol on initiation of esophageal tumorigenesis by diethylnitrosamine (DEN) were investigated in male F344 rats. Animals were administered 50 p.p.m. DEN plus 10% ethanol (Group 1), 33 p.p.m. DEN (Group 2), 50 p.p.m. DEN (Group 3) or 10% ethanol (Group 4) in the drinking water for the first 8 weeks, and were then maintained on basal diet and tap water for up to 104 weeks. The concentration of 33 p.p.m. DEN in Group 2 was an adjustment to the anticipated intake in Group 1. Consequent total intakes of DEN in Groups 2 and 3 were respectively 80% and 134% of that in Group 1. Histopathological examination of esophagus tissue after final sacrifice revealed incidences of papillomas and/or carcinomas in Groups 1, 2 and 3 to be 57.7, 3.8 and 10.7% respectively. No esophageal tumors occurred in Group 4. The incidence of hyperplasia was 100% in Group 1 in contrast to 46.2% in Group 2, 57.1% in Group 3 and 3.6% in Group 4. Thus, the incidences of esophageal proliferative lesions were significantly higher in Group 1 than in Groups 2 or 3. Our results clearly indicate that ethanol has an enhancing effect on the development of esophageal tumors induced by DEN in rats, when administered during the initiation phase.