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Neoplasms in Purebred Boxer Dogs following Long-Term Administration of N-Methyl-N-nitrosourea¹

Department of Veterinary Pathobiology, The Ohio State University, Columbus, Ohio 43210

The carcinogenicity of N-methyl-N-nitrosourea (MNU) has been demonstrated in several species for a variety of tissues, particularly the nervous system. Boxer dogs, a breed with a high incidence of spontaneous tumors (including brain tumors), were exposed to MNU to determine their susceptibility to MNU and to compare the induced tumors with the types of tumors reported in the literature.

Twenty purebred Boxer dogs were given weekly i.v. injections of MNU, 5 mg/kg, for 36 weeks and were observed for approximately 3 years for the development of neoplasia. Nineteen of 20 dogs developed neoplasms 19 to 36.5 months after the first injection. The mean latent period was 30 ± 5 (S.D.) months. All tumor-bearing dogs had 2 or more neoplasms, including metastases, and 14 dogs had tumors of more than 1 tumor type. Malignant neurinomas of the small intestine were present in 11 dogs, and poorly differentiated sarcomas of the small intestine were found in 6 dogs. Metastasis occurred to liver, spleen, lymph nodes, lung, and adrenal. Two cases of malignant neurinoma developed in the heart, and 1 each developed in the stomach and colon. Two welldifferentiated neurinomas occurred in the small intestine, and 1 each occurred in a spinal root, the stomach, and the colon.

The high incidence rate, young age of development, and unique tumor types clearly distinguished the tumors from spontaneous tumors of Boxers. Although the lack of brain involvement was unexplained, MNU had a neurooncogenic effect on the peripheral nerves of the gastrointestinal tract.

¹ Supported in part by Grants CA11224, RR05463, and GM1052 from the NIH. Presented in part at the annual meeting of the American Association for Cancer Research, Toronto, Ontario, Canada, May 1976 (9).

² Present address: Pathology and Toxicology Research Unit, The Upjohn Company, Kalamazoo, Mich. 49001.

³ To whom requests for reprints should be addressed, at Pathology and Toxicology Research Unit, The Upjohn Co., 301 Henrietta Street, Kalamazoo, Mich. 49001.

Received 12/12/77. Accepted 3/14/78.