Promotion of chemically induced rat esophageal tumorigenesis with post-initiation ethanol modification

Post-initiation ethanol modification on N-nitrosomethylbenzylamine (NMBA)-i nduced rat esophageal carcinogenesis model was investigated in male, 6-week -old, F344 rats that received s.c. injections, 3 times per week, of 0.5 mg/ kg NMBA for the first 5 weeks and then were treated with 0% (Group1), 3.3% (Group2), and 10% (Group3) ethanol in the drinking water for up to 20 weeks . Group 4 received 10% ethanol without NMBA administration and Group 5 was maintained without any chemical treatment. There were no statistical differ ences in the incidence and multiplicity of esophageal tumors among Groups 1 to 3. However, the multiplicity of hyperplasias was statistically greater in Group 3 than in Groups I or 2. Esophageal epithelia of all rats in Group s 4 and 5 demonstrated a normal histology. BrdU labelling indices of tumors and hyperplasias in NMBA-treated groups were essentially similar, although cycline D1 was overexpressed to a greater extent in tumors and also hyperp lasias of Group 3 than in Groups 1 or 2. The results indicated ethanol to e xert weak promotion effects through cycline D1 overexpression on rat esopha geal tumorigenesis initiated with NMBA. (C) 2001 Wiley-Liss, Inc.