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

Teratog Carcinog Mutagen. 2001;21(4):295-301. doi: 10.1002/tcm.1017.

Abstract

Post-initiation ethanol modification on N-nitrosomethylbenzylamine (NMBA)-induced 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% (Group 1), 3.3% (Group 2), and 10% (Group 3) 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 differences 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 1 or 2. Esophageal epithelia of all rats in Groups 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 hyperplasias of Group 3 than in Groups 1 or 2. The results indicated ethanol to exert weak promotion effects through cycline D1 overexpression on rat esophageal tumorigenesis initiated with NMBA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Carcinogens
  • Cyclin D1 / metabolism
  • Dimethylnitrosamine / analogs & derivatives
  • Disease Progression
  • Epithelium / drug effects
  • Esophageal Neoplasms / chemically induced*
  • Esophagus / drug effects
  • Ethanol / toxicity*
  • Hyperplasia
  • Immunohistochemistry
  • Male
  • Rats
  • Rats, Inbred F344

Substances

  • Carcinogens
  • Cyclin D1
  • Ethanol
  • nitrosobenzylmethylamine
  • Bromodeoxyuridine
  • Dimethylnitrosamine