Dependence of Tumor Spectrum on Route of Administration in Sprague-Dawley Rats as a Result of Single or Multiple Injections of Methyl(acetoxymethyl)nitrosamine2

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Abstract
Methyl(acetoxymethyl)nitrosamine (DMN-OAc). which selectively induces intestinal tumors in rats when injected ip, was administered by different routes (iv, orally, sc, and ip) in single and multiple treatments and in both aqueous and nonaqueous vehicles to groups of 30 noninbred Sprague-Dawley (Charles River CD) rats. Five-week-old rats were administered 0.10 mmole DMN-OAc/kg body weight, which is one-half the acute ip median lethal dose, as a single dose via the various routes indicated. Rats given multiple ip or sc administrations received either 0.02 or 0.04 mmole DMN-OAc/kg per injection. Males only were used in each study; however, in the studies in which single ip injections were given, both sexes were used. Single ip injections of 0.1 mmole DMN-OAc/kg resulted in a high incidence of epithelial tumors of the intestinal tract in rats of both sexes. Males developed more tumors; 70 tumors were observed in 29 males versus 41 tumors in 29 females. Doubling the dose and dividing it into multiple ip injections increased the incidence of epithelial tumors of the intestines. Five injections of 0.04 mmole/kg resulted in 168 intestinal tumors in 29 male rats. In rats treated ip a significant incidence of nervous system tumors was found, principally schwannomas arising from small nerves in the serosae of abdominal organs. Treatment by routes other than ip virtually eliminated the selectivity of DMN-OAc for the intestines. Single oral administrations of 0.1 mmole DMNOAc/kg dissolved in buffer or vegetable on resulted in high yields of stomach tumors, many of which were adenocarcinomas. Few tumors were induced elsewhere, and the vehicle of administration had little effect on tumor yield or type. Single or multiple sc injections of DMN-OAc produced a high yield of mammary and soft tissue tumors at the site of injection, as well as a significant incidence of tumors at distant sites, especially the lungs and Zymbal's glands. Single iv injections of 0.1 mmole DMN-OAc/kg resulted in a high yield of lung, Zymbal gland, and nervous system tumors, particularly endocardial neurinomas.

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