The incidences of lung tumors and thymic lymphomas were increased in young adult male RF mice receiving 30 milligrams of methyl meth anesulfonate per kilogram of body weight daily in the drinking water throughout life. Differences in oncogenicity between treatment with methyl methanesulfonate and with dimethylnitrosamine or diethylnitrosamine suggest a qualitative difference between the site (or sites) of alkylation by methyl methanesulfonate and by dimethylnitrosamine or diethylnitrosamine within the nucleic acids.
Diethylnitrosamine ( D E N ) was given to male RF mice in the drinking (Clapp and Craig, 1967). Although the primary target organ in most species is the liver, DEN induces squamous cell carcinomas of the forestomach, lung adenomas, and liver hepatomas in the male RF mouse (Clapp and Craig, 1967).Druckrey and co-workers reported an inverse correlation between mean cumulative dose and mean induction time of several carcinogens, including DEN (Druckrey and Schmahl, 1962; Druckrey et al., 1963b), and their reports have been confirmed by others (Schmahl and Thomas, 1965;Rajewsky et al., 1966). No evidence of a threshold dose was found for DEN in liver and esophageal carcinomata, and the mean total carcinogenic dose of DEN decreased with lower daily doses over correspondingly extended test periods (Druckrey et al., 19633). They observed a change in the target organ with varied daily doses of DEN: high doses given singly or in a few oral treatments yielded kidney tumors, low daily doses yielded esophageal and liver tumors, and intermediate doses yielded only liver tumors (Druckrey et al., I963a).Since DEN has shown a unique organ affinity in R F mice as compared with other species and strains, we sought to determine the relationships between total dose of DEN and tumor induction in the lung, liver, and forestomach. Although daily dose rate may modify the oncogenic process,
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