Summary
The homologons alkyl-acetoxymethyl-nitrosamines were tested for carcinogenicity in SD rats. All compounds were found to be carcinogenic and induced within the same time carcinomas of the forestomach. The total doses necessary for induction of tumors are related to the length of the alkyl chain and hence to the watersolubility. These results are discussed.
Zusammenfassung
Die homologe Reihe der Alkyl-Acetoxymethyl-Nitrosamine wurden auf ihre carcinogene Wirkung an SD Ratten getestet. Alle Verbindungen induzieren bei oraler Gabe innerhalb der gleichen Zeit Vormagentoumoren. Die benötigten Gesamtdosen sind dabei abhängig von der Länge der Alkyl-Kette und damit der Wasserlöslichkeit. Diese Ergebnisse werden diskutiert.
Similar content being viewed by others
Literatur
Camus,A.M., Wiessler,M, Malaveille,C., Bartsch,H.: High mutagenicity of N. Mutation Research (1977)
Cotrell,R.C, Lake,B.G., Phillips,J.C., Gangolli,S.D.: Metabolic Degradation of Stable Isotope Labelled Dimethylnitrosamine by Rat Liver. Biochem. Soc. Trans. 5, 311–312 (1977)
Cotrell,R.C, Lake,B.G., Phillips,J.C., Gangolli,S.D.: The hepatic metabolism of 15N-labelled Dimethylnitrosamine in the rat. Biochem. Pharm. 26, 809–813 (1977)
Czygan,P., Greim,H., Garro,A.J., Hutterer,F., Schaffner, F., Popper, H., Rosenthal, O., Cooper, D.Y.: Microsomal Metabolism of Dimethylnitrosamine and the Cytochrome p-450 Dependency of its.Activation to a Mutagen. Cancer Res. 33, 2983–2986 (1973)
Fahmy,O.G., Fahmy, M.J., Wiessler, M.: α-Acetoxy-dimethylnitrosamine: A proximate metabolite of the carcinogenic Amine. Biochem. Pharmacol. 24, 1145–1148 (1975)
Joshi,S.R., Rice,J.M., Wenk,M.L., Roller,P.P., Keefer, L.K.: Selective induction of intenstinal tumors in rats by methyl (acetoxymethyl) nitrosamine, an Ester of the presumed reactive metabolite. J. Natl. Cancer Inst. 58, 1531–1534 (1977)
Kim,S., Lotlikar,P.D., Chin,W., Magee,P.N.: Protein bound Carboxymethylester as a precursor of methanol formation during oxidation of dimethylnitrosamine in vitro. Cancer Letters 2, 279–284 (1977)
Kleihues,P., Cooper,H.K., Repair excision of alkylated Bases from DNA in vivo. Oncology 33, 86–88 (1976)
Krüger,F.W.: Metabolismus von Nitrosaminen in vivo I. Über die β-Oxidation aliphatischer Di-nalkylnitrosamine. Z. Krebsforsch. 76, 145–154 (1971)
Lijinsky,W., Taylor,H.W.: Carcinogenicity of Nitrosoazetidine and Tetradeuteronitroso-azetidine in Sprague-Dawley Rats. Z. Krebsforsch. 89, 215–219 (1977)
Magee,P.N., Barnes,J.M: Carcinogenic Nitroso Compounds. Advances Cancer Res. 10, 163–246 (1967)
Okada,M., Suziki,E., Anjo,T., Mochizuki.M.: Mutagenicity of β-acetoxy-dialkylnitrosamines: model compounds for an ultimate carcinogen. Gann 66, 457–458 (1975)
Pegg,A.E., Jackson,A.: Alkylation of messenger RNA by dimethylnitrosamine. Chem.-Biol. Interactions 12, 279–284 (1976)
Roller,D.P., Shimp,D.R., Keefer,L.K.: Synthesis and solvolysis of methylacetoxymethylnitrosamine to the presumed carcinogenic metabolite of dimethylnitrosamine. THL 2065-2068 (1975)
Swann,P.F., Magee,P.N.: The nitrosamine-Induced Carcinogenesis of Nucleic Acids of the rat by N-Methyl-N-Nitrosourea, Dimethylnitrosamine, Dimethylsulfate and Methylmethansulfonate. Biochem. J. 110, 39–47 (1968)
Swenson,D.H., Farmer,P.B., Lawley,P.D.: Identification of Thymidylyl(3′-5′) Thymidine as a product from reaction of DNA with the carcinogen N-Methyl-N-Nitrosourea. Chem.-Biol. Interactions 15, 91–100 (1976)
Wiessler,M.: Synthese α-funktioneller Nitrosamine. Angew. Chem. 68, 817–818 (1974)
Wiessler,M., Schmähl,D.: Zur carcinogenen Wirkung von N-Nitroso-Verbindungen. 5. Mitteilung: Acetoxymethal-Methyl-Nitrosamin. Z. Krebsforsch. 85, 47–49 (1976)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wiessler, M., Habs, M. & Schmähl, D. Zur carcinogenen Wirkung von N-Nitroso-Verbindungen. Z. Krebsforsch. 91, 317–322 (1978). https://doi.org/10.1007/BF00312293
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00312293