ICRC mouse with congenital mega-esophagus as a model to study esophageal tumorigenesis

ICRC mouse, an inbred strain, developed at the Cancer Research Institute, Bombay, exhibits mega-esophagus with markedly hyperplastic mucosa. Diethylnitrosamine (DEN) when given in drinking water at the dose of 4 mg/kg body weight/day, induced esophageal papillomas consistently in 100% of the animals, in a short period of 12 weeks. Further, tumors were produced, even at a very low cumulative dose of 28 mg/kg body weight. Development of the esophageal papillomas was dose dependent. DEN even induces esophageal tumors transplacentally in the ICRC F1 progeny. Tobacco acts predominantly as a promoter in this system. ICRC mouse thus provides a much needed animal model to study esophageal tumorigenesis, including the two-stage carcinogenesis. An interesting feature of the study is that initiation could be induced by exposure to low doses of DEN in the intra-uterine life. Tumors develop in such F1 animals only if they are fed tobacco, a predominant promoter, post-natally.