Summary
Two groups of 75 rats were injected intraperitoneally with one single dose of 9 mg/kg DMNA and 120 mg/kg DENA, respectively, 28 h after partial hepatectomy. Control groups of non-hepatectomized rats received one single injection of DMNA or DENA at doses of 20 mg/kg and 200 mg/kg, respectively, which were found to be equitoxic to the doses administered to partially hepatectomized rats. One control group of partially hepatectomized rats was injected with saline. Tumors developed in the partially hepatectomized rats injected with nitrosamines with the following frequency: for DMNA: 13% in the liver, 13% in kidney, 4% in lung, 4% at the surgical scar, 9% in hematopoietic tissue and 13% in other organs; for DENA: 11% in liver, 27% in the kidney, 2% at the surgical scar, 2% in hematopoietic tissue, and 11% in other organs. The histological characteristics of these tumors are described. Statistical analysis of the results shows that no significant difference exists in the overall tumor incidence induced by DMNA and DENA and that the difference between liver and kidney tumors induced by DENA is significant, whereas the difference between DMNA- and DENA-induced kidney tumors is less significant. When analyzed by t-test, our results show that death from tumors occurred at an earlier time after DENA than after DMNA treatment and that liver tumors appeared at a significantly earlier time after DENA than after DMNA treatment. Tumors appearing in the same experimental group display similar mean induction times.
The possible correlation between metabolic half-life of each nitrosamine in the body and their respective carcinogenic power is discussed.
The longer half-life of DENA may be responsible for the shorter tumor induction time observed for this drug, compared to DMNA. The liver tumor incidence, on the other hand, seems to be independent of the half-life but strongly determined by the fact that the proximate carcinogen reaches the hepatic cell during the DNA synthesis phase.
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Fridman-Manduzio, A., Gol-Winkler, R., Betz, E.H. et al. Tumor frequency and characteristics after a single dose of dimethylnitrosamine or diethylnitrosamine in partially hepatectomized rats. Z. Krebsforsch. 90, 13–24 (1977). https://doi.org/10.1007/BF00306018
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DOI: https://doi.org/10.1007/BF00306018