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.
Hecht
S S
SS
NCI-Frederick Cancer Research Facility, MD 21701.
Lijinsky
W
W
Kovatch
R M
RM
Chung
F L
FL
Saavedra
J E
JE
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D006394:Hemangiosarcoma / Q000139:chemically induced / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D009374:Neoplasms, Experimental / Q000473:pathology*; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013964:Thyroid Neoplasms / Q000139:chemically induced / Q000473:pathology
D002273:Carcinogens; D009602:Nitrosamines; C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; C002741:N-nitrosomorpholine; C043883:N-nitroso-2-hydroxymorpholine