Comparative tumorigenicity of N-nitroso-2-hydroxymorpholine, N-nitrosodiethanolamine and N-nitrosomorpholine in A/J mice and F344 rats.

N-Nitroso-2-hydroxymorpholine (NHMOR), a genotoxic metabolite of the environmental carcinogens N-nitrosomorpholine (NMOR) and N-nitrosodiethanolamine (NDELA), was assayed for tumorigenicity in A/J mice and F344 rats. Groups of female mice were given NHMOR, NMOR or NDELA in the drinking water over a 10-week period; total doses were 53-55 mumol/mouse. The experiment was terminated after 30 weeks. Whereas NMOR was a potent tumorigen, inducing 20.3 lung tumors/mouse, NHMOR and NDELA were only weakly tumorigenic, giving 1.2 and 1.4 lung tumors/mouse respectively. Groups of female F344 rats were also given these three nitrosamines in drinking water for 50 weeks, as follows: NHMOR, total dose 0.6 mmol/rat; NHMOR, 1.2 mmol; NMOR, 1.1 mmol and NDELA, 5.6 mmol. The experiment was terminated after 120 weeks. NMOR was a potent carcinogen, inducing liver tumors in 100% of the rats. NDELA gave hepatocellular tumors in 70% of the rats. NHMOR was inactive even at the higher dose. The results of this study do not support the hypothesis that NHMOR is a proximate carcinogen of NDELA or NMOR.

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