Summary
Radioactivity in liver nucleic acids increased to a plateau in one week, and decreased slightly after 3 weeks. Radioactivity of nucleic acids in the lungs and kidneys was less than that of liver nucleic acids for the first week, but then gradually increased to the same level as the latter. However, the amount of N7-methylguanine in nucleic acids was 2 to 4 times more in the liver than in the kidneys and lungs after 30 days. The maximal level of N7-methylguanine in DNA was found after 21 days, when approximately 0.1% of guanine residues in liver DNA were methylated. Maximum methylation of RNA was also observed after 21 days. Initially methylation of liver ∼4S RNA was more than that of ribosomal RNA, but later the extents of methylation to the cytoplasmic RNA species became similar.
Zusammenfassung
Die Aktivität der Nucleinsäuren stieg in der Leber in einer Woche zu einem Plateau an und nahm nach 3 Wochen wieder leicht ab, in Lungen und Nieren war sie in der ersten Woche geringer als in der Leber, stieg aber später zur selben Höhe wie in der Leber. Die Menge von N7-Methylguanin in den Nucleinsäuren war jedoch nach 30 Tagen in der Leber 2-bis 4mal größer als in Nieren und Lunge. Der höchste Spiegel von N7-Methylguanin in DNS fand sich nach 21 Tagen, wenn etwa 0.1% der Guaninreste in der Leber DNS methyliert waren. Maximale Methylierung der RNS wurde ebenfalls nach 21 Tagen beobachtet. Die anfängliche Methylierung von ∼4S RNA1 war größer als die der ribosomalen RNS; später wurde das Ausmaß der Methylierung ähnlich dem der cytoplasmatischen RNS.
Similar content being viewed by others
Abbreviations
- DMN:
-
dimethylnitrosamine
- EDTA:
-
ethylenediaminetetraacetic acid disodium
- SSC:
-
0.15 M NaCl-0.015 M sodium citrate
References
Agarwal,M.K., Weinstein,I.B.: Modifications of ribonuoleic acid by chemical carcinogens. II. In vivo reaction of N-2-acetylaminofIuorene with rat liver ribonucleic acid. Biochemistry 9, 503–508 (1970)
Chauveau,J., Moulé,Y., Rouiller,C.: Isolation of pure and unaltered liver nuclei, morphology and biochemical composition. Exp. Cell Res. 11, 317–321 (1956)
Clapp,N.K., Craig,A.W., Toya,R.E.: Pulmonary and hepatic oncogenesis during treatment of male RF mice with dimethylnitrosamine. J. nat. Cancer Inst. 41, 1213–1227 (1968)
Den Engelse,L., Bentvelzen,P.A.J., Emmelot,P.: Studies on lung tumours. I. Methylation of deoxyribonucleic acids and tumour formation following administration of dimethylnitrosamine to mice. Chem.-Biol. Interactions 1, 395–406 (1969/70)
Den Engelse,L., Emmelot,P.: Effects of feeding the carcinogen dimethylnitrosamine on its metabolism and methylation of DNA in the mouse. Chem.-Biol. Interactions 4, 321–327 (1971/72)
Irving,C.C., Veazey,R.A.: Preferential binding of 2-acetylaminofluorene to rat liver rRNA during early stages of hepatocarcinogenesis. Biochem. Biophys. Res. Commun. 47, 1159–1164 (1972)
Irving,C.C., Veazey,R.A., Williard,R.F.: On the significance and mechanism of the binding of 2-acetylaminofluorene and N-hydroxy-2-acetylaminofluorene to rat liver ribonucleic acid in vivo. Cancer Res. 27, 720–725 (1967)
Lawley,P.D.: The action of alkylating mutagens and carcinogens on nucleic acids: N-Methyl-N-nitroso compounds as methylating agents. In: Nakahara,W., Takayama,S., Sugimura,T., Odashima,S. (Eds.): Topics in Chemical Carcinogenesis. pp. 237–258. Univ. Tokyo Press (Tokyo) 1972
Lawley,P.D., Brookes,P., Magee,P.N., Craddock,V.M., Swann,P.F.: Methylated bases in liver nucleic acids from rats treated with dimethylnitrosamine. Biochim. biophys. Acta (Amst.) 157, 646–648 (1968)
Lee,K.Y., Lijinsky,W., Magee,P.N.: Methylation of ribonucleic acids of liver and other organs in different species treated with C14- and H3-dimethylnitrosamine in vivo. J. nat. Cancer Inst. 32, 65–76 (1964)
Loveless,A.: Possible relevance of 0–6 alkylation of deoxyguanosine to mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature (Lond.) 223, 206–207 (1969)
Magee,P.N., Barnes,J.M.: The production of malignant primary hepatic tumours in the rat by feeding dimethylnitrosamine. Brit. J. Cancer 10, 114–122 (1956)
Magee,P.N., Barnes,J.M.: Induction of kidney tumours in the rat with dimethylnitrosamine (N-nitrosodimethylamine). J. Path. Bact. 84, 19–31 (1962)
Magee,P.N., Farber,E.: Toxic liver injury and carcinogenesis; methylation of rat liver nucleic acid by dimethylnitrosamine in vivo. Biochem. J. 83, 114–124 (1962)
Marmur,J.: A procedure for the isolation of deoxyribonucleic acid from microorganisms. J. molec. Biol. 3, 208–218 (1961)
Muramatsu,M., Azama,Y., Nemoto,N., Takayama,S.: Methylation of nuclear and cytoplasmic RNA of mouse liver with dimethylnitrosamine-3H. Cancer Res. 32, 702–709 (1972)
Swann,P.F., Magee,P.N.: Nitrosamine-induced carcinogenesis. The alkylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate. Biochem. J. 110, 39–47 (1968)
Takayama,S., Oota,K.: Malignant tumours induced in mice fed with N-nitrosodimethylamine. Gann 54, 465–472 (1963)
Terracini,B., Magee,P.N.: Renal tumours in rats following injection of dimethylnitrosamine. Nature (Lond.) 202, 502–503 (1964)
Terracini,B., Magee,P.N., Barnes,J.M.: Hepatic pathology in rats on low dietry levels of dimethylnitrosamine. Brit. J. Cancer 21, 559–565 (1967)
Toth,B., Magee,P.N., Shubik, P.: Carcinogenesis study with dimethylnitrosamine administered orally to adult and subcutaneously to newborn BALB/c mice. Cancer Res. 24, 1712–1721 (1964)
Author information
Authors and Affiliations
Additional information
This work was partly supported by a grant from the Ministry of Education of Japan.
Rights and permissions
About this article
Cite this article
Nemoto, N., Takayama, S. Formation of N7-methylguanine in nuclear DNA and cytoplasmic RNA in mice on continuous oral administration of dimethylnitrosamine-3H solution. Z. Krebsforsch. 80, 113–125 (1973). https://doi.org/10.1007/BF00305130
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00305130