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Diethylnitrosamine oncogenesis in RF mice as influenced by variations in cumulative dose
Author(s) -
Clapp N. K.,
Craig A. W.,
Toya R. E.
Publication year - 1970
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910050116
Subject(s) - stomach , carcinogenesis , lung , incidence (geometry) , cumulative dose , medicine , cumulative incidence , gastroenterology , lymphoma , body weight , endocrinology , physiology , pathology , cancer , transplantation , optics , physics
Diethylnitrosamine (DEN) was given to male RF mice in the drinking water at levels of 2–11.5 mg/kg body weight daily for varying periods; cumulative doses ranged from 57 to 943 mg/kg body weight. In all treated groups, incidences of lung adenomas, hepatomas, and forestomach squamous cell carcinomas exceeded those in controls; maximum incidences reached 84%, 98%, and 100%, respectively, as compared with control values of 41%, 5%, and 0%. At lower doses, incidence of liver tumors increased linearly with dose, reaching 80–90% at DEN doses of 300 mg/kg and above, whereas the lowest dose of DEN induced a maximum incidence of lung tumors. Only at the lowest dose did DEN fail to induce a maximum incidence of stomach tumors. The mean survival time, mean age at death with all types of tumors, and minimum induction times decreased with increasing dose. DEN did not exert a leukemogenic effect at the doses used, and an inhibitory effect is even suggested: only 1/371 (0.3%) DEN‐treated mice developed myeloid leukemia and 4/371 (1%) thymic lymphoma, compared with control values of 7/162 (4%) and 6/162 (3.7%), respectively. At the lowest dose used, the lung appears most sensitive (maximum tumor induction), the stomach intermediate in sensitivity, and the liver least sensitive to DEN‐oncogenesis.