Carcinogenesis and nucleic acid alkylation by some oxygenated nitrosamines in rats and hamsters.
A comparison has been made of the carcinogenic effects of nitroso-2,6-dimethylmorpholine and several hydroxylated acyclic nitrosodialkylamines derived from it or related to it in rats and Syrian hamsters. In rats nitrosodimethylmorpholine was the most potent, inducing mainly esophageal tumors. Nitrosodiethanolamine was the weakest of the five nitrosamines in both rats and hamsters. Tumors of the pancreas ducts were induced by four of the five compounds, but only in hamsters, and esophageal tumors appeared only in rats. Most of the nitrosamines induced tumors of liver and lung in both rats and hamsters. A study of alkylation of nucleic acids of the liver following treatment of rats and hamsters with the radiolabeled nitrosamines showed that nitrosodiethanolamine alkylated liver nucleic acids in rats to only a very small extent. The other four nitrosamines all gave rise to 7-methylation and O6-methylation of guanine residues in DNA of hamster liver and all but nitrosodimethylmorpholine in rat liver DNA, which corresponded quite well with the induction of liver tumors in the two species. Quantitatively, however, there was not a good correlation between liver DNA alkylation and the potency of the nitrosamine in inducing tumors.
Lijinsky
W
W
NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, MD 21701.
Saavedra
J E
JE
Kovatch
R M
RM
D000284:Administration, Oral; D000478:Alkylation; D000818:Animals; D006224:Cricetinae; D004247:DNA / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008113:Liver Neoplasms / Q000139:chemically induced; D008745:Methylation; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009602:Nitrosamines / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013270:Stomach
D009602:Nitrosamines; C014130:N-nitroso-2,6-dimethylmorpholine; C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; C012457:diisopropanolnitrosamine; C013622:nitrosobis(2-oxopropyl)amine; C013624:N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine; D004247:DNA