Evidence of formation of N‐methyl‐N‐nitrosourea in rats given n‐methylurea and sodium nitrite

Abstract

N[14C]-methylurea and sodium nitrite were administered simultaneoussly to rats by stomach tube in order to demonstrate methylation of the nucleic acids due tojhe formation in the stomach of the corresponding nitrosamide, N[14C]-methyl-N-nitrosourea. The ion-exchange chromatograms of the hydroiysates of stomach, liver and small intestine nucleic acids show a radioactive peak corresponding to the altered base 7-methylguanine in the rat receiving N[14C]-methylurea and sodium nitrite. No evidence of 7-methylguanine was obtained when N[W]-methylurea was administered alone. These findings are interpreted as indicating that the highly potent carcinogen N-methyl-N-nitrosourea is formed in the stomach as a result of the nitrosation of the corresponding secondary amide and absorbed into the circulation of the rat. The possible consequences of the in vivo formation of carcinogenic N-nitroso compounds in the aetiology of cancer are discussed. ~~ ~ De la N[14C]-mCthylur&e et du nitrite de sodium ont &ti administris sirnultantment a des rats a I'aide d'une sonde stomacale en vue d'observer la mtthylution des acides nucliiques due a la formation duns l'estomac du nitrosamide correspondant: N[14C]-mtthyl-N-nitrosourte. Les chromatogrammes d'tchanges ioniques des hydrolysats des acides nucliiques de I'estomuc, du foie et de I'intestin grgle rivtlent un maximum radioactif qui correspond a la base 7-mithylguanine altirte chez le rat ayant

Transplacental induction of lymphomas in Swiss mice by carbendazim and sodium nitrite

“…The formation of N-nitroso compounds from secondary and tertiary amines, and alkyl-urea derivatives under acidic conditions, is evident from both in vitro and in vivo studies (Greenblatt et al, 1971; Magee and Barnes, 1967;Mirvish, 1971; Montesano and Magee, 1971 ;Sander et al, 1968). The importance of this interaction in relation to human cancer has been emphasized by several authors (Endo et al, 1973;Hill et al, 1973;Mirvish, 1975;Sander 1967).…”

The effects of diethylnitrosamine on ribonucleic acid and protein synthesis in the liver and lung of the Syrian golden hamster

“…A correlation apparently exists between breakdown and acute toxic effects, such as cell death (Magee & Barnes, 1967;Magee & Swann, 1969). A most important finding was the observation by Montesano & Magee (1971) that slices from hamster lung are as active as slices from hamster liver in the production of 14CO2 on incubation with [14C]diethylnitrosamine. This could imply that hamster lung has a similar capacity to that of liver 1973 for metabolizing diethylnitrosamine.…”

Detection of 8 azaguanine resistant mutants of embryonic cells induced by products formed in the stomach on oral administration of sodium nitrite plus aminopyrine to pregnant golden hamsters.

“…Aminopyrine, a secondary amine, has been widely used throughout the world as an antifebrile drug and the presence of sodium nitrite in food additives and drinking water has been known (Carosby et al, 1972;Fario et al, 1971;Wolff and Wasserman, 1972). The possible risk to human health on exposure to environmental nitroso-compounds or their precursors has been discussed (Mirvish, 1971;Montesano and Magee, 1971;Wolff and Wasserman, 1972). Evidence for the danger of nitroso-compounds has been presented to show that potentially carcinogenic nitrosamines are formed from secondary amines and nitrite in the stomach of laboratory animals and man (Mirvish, 1970;Montesano and Magee, 1971), and that rats and mice fed on diet containing sodium nitrite and secondary amines have developed tumors (Sander andBurkel, 1969, 1971;Lijinsky et al, 1973) .…”

“…The possible risk to human health on exposure to environmental nitroso-compounds or their precursors has been discussed (Mirvish, 1971;Montesano and Magee, 1971;Wolff and Wasserman, 1972). Evidence for the danger of nitroso-compounds has been presented to show that potentially carcinogenic nitrosamines are formed from secondary amines and nitrite in the stomach of laboratory animals and man (Mirvish, 1970;Montesano and Magee, 1971), and that rats and mice fed on diet containing sodium nitrite and secondary amines have developed tumors (Sander andBurkel, 1969, 1971;Lijinsky et al, 1973) . At present, procedures have remained unsatisfactorily for detecting carcinogenic substances produced from two or more non-carcinogenic or non-mutagenic chemicals in vivo except assay of chemical carcinogenesis in viva (Couch and Friedman, 1975;Braun et al, 1977;Inui et al, 1978).…”