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Induction of Adenocarcinomas of the Colon in Mice by Weekly Injections of 1,2-Dimethylhydrazine¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and the Cornell University Medical College, New York, New York 10021

Thirty-four CF1 mice were given weekly s.c. injections of 20 mg of 1,2-dimethylhydrazine hydrochloride per kg; this treatment induced colonic carcinomas in more than 90% of the animals after 186 days. The earliest change was found to be a widening of the proliferative compartment within the colonic crypts; at a later stage, there was an increase of the tritiated thymidine-labeling index from 9.3% at Day 45 to 16.2% at Day 87. The first histological changes were focal hyperplastic changes and focal atypias on the tip of the folds of the distal colonic mucosa (Day 38) confined to single crypts. The colonic tumors were located in the distal colon and rectum, with a high incidence of squamous cell cancers originating from the anal canal. Saline extracts of colonic tumor material precipitated specific antimouse embryonic rabbit serum. Assays of hypoxanthine phosphoribosyltransferase in the villus fraction of the small bowel of the 1,2-dimethylhydrazine hydrochloride-treated tumor-carrier mice indicated lower activity, compared to that of controls.

¹ This work was supported in part by National Cancer Institute Grants Ca 08748 and 08921, Contract 72-2041, and a Swiss National Fund Fellowship. Presented in abstract form at the 63rd Meeting of the American Association for Cancer Research, May 1972.

² Present address: Mediz. Universitatsklinik, Basel, Switzerland.

³ To whom correspondence should be addressed, at the Sloan-Kettering Institute for Cancer Research, New York, N. Y. 10021.

Received 10/12/72. Accepted 1/24/73.

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