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Natural History of Intestinal Neoplasms Induced in Rats by a Single Injection of Methyl(acetoxymethyl)nitrosamine¹

National Cancer Institute [J. M. W., J. M. R., P. P. R.], Bethesda 20014, and Microbiological Associates [M. L. W.], Bethesda, Maryland 20016

Male Sprague-Dawley-derived rats (Charles River CD) were injected once i.p. at 5 weeks of age with methyl-(acetoxymethyl)nitrosamine at a dose level of 0.1 mmole/kg (one-half of the 50% lethal dose). Groups of 27 to 30 rats were sacrificed 20, 25, 30, 40, and 50 weeks later to study the development and natural history of induced tumors of the intestines. An additional 30 rats were allowed to die or were killed in poor condition. From 70 to 90% of the rats developed tumors from 20 to 50 weeks after injection, and 70 to 86% of the rats had intestinal tumors, most commonly in the small intestine. Most tumors of the small intestine were tubular adenocarcinomas that progressively invaded the gut wall. Tumor size correlated with degree of invasion of extramucosal tissues. As they grew large, these tumors developed cystic spaces and foci of stromal osteoid metaplasia. Such cystadenocarcinomas rarely metastasized despite their large size. Stromal lymphoid reaction was frequently observed. Four of 14 mucinous (signet ring) adenocarcinomas orginating in the small intestine metastasized to the peritoneal cavity. Colon tumors occurred more variably in 6 to 42% of rats in different groups and were usually polypoid adenocarcinomas that never invaded the tunica muscularis. Only a few invasive tubular adenocarcinomas were seen. The carcinogen also induced other tumors in the peritoneal cavity and abdominal viscera in low incidence, including sarcomas, mesotheliomas, lymphangiomas, renal tumors, carcinomas of the seminal vesicles, and, occasionally, tumors of other tissues.

¹ Supported in part by UPHS Contract NO1-CP-02199 to Microbiological Associates and GSA Contract 00S-31212 to Baker Histology Laboratories, Great Falls, Va.

² To whom requests for reprints should be addressed.

Received 2/28/77. Accepted 6/ 1/77.

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