Abstract
1. The extent of ethylation of N-7 of guanine in the nucleic acids of rat tissue in vivo by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate was measured. 2. All compounds produced measurable amounts of 7-ethyl-guanine. 3. A single dose of diethylnitrosamine or N-ethyl-N-nitrosourea produced tumours of the kidney in the rat. Three doses of ethyl methanesulphonate produced kidney tumours, but a single dose did not. 4. A single dose of diethylnitrosamine produced twice as much ethylation of N-7 of guanine in DNA of kidney as did N-ethyl-N-nitrosourea. A single dose of both compounds induced kidney tumours, although of a different histological type. 5. A single dose of ethyl methanesulphonate produced ten times as much ethylation of N-7 of guanine in kidney DNA as did N-ethyl-N-nitrosourea without producing tumours. 6. The relevance of these findings to the hypothesis that alkylation of a cellular component is the mechanism of induction of tumours by nitroso compounds is discussed.
Full text
PDF![841](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de8/1178189/c17114d8cf30/biochemj00641-0179.png)
![842](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de8/1178189/41bf6bfe2cbd/biochemj00641-0180.png)
![843](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de8/1178189/ab79ae4bd448/biochemj00641-0181.png)
![844](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de8/1178189/94ed16c96e15/biochemj00641-0182.png)
![845](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de8/1178189/fe554dbc22ce/biochemj00641-0183.png)
![846](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de8/1178189/df0c09205c15/biochemj00641-0184.png)
![847](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de8/1178189/c27b42cb2f50/biochemj00641-0185.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alexandrov V. A. Uterine, vaginal and mammary tumours induced by nitrosoureas in pregnant rats. Nature. 1969 Jun 14;222(5198):1064–1065. doi: 10.1038/2221064a0. [DOI] [PubMed] [Google Scholar]
- DONTENWILL W., MOHR U., ZAGEL M. [On the different effect in lung carcinoma of diethylnitrosamine in hamsters and rats]. Z Krebsforsch. 1962;64:499–502. [PubMed] [Google Scholar]
- DRUCKREY H., SCHILDBACH A., SCHMAEHL D., PREUSSMANN R., IVANKOVIC S. QUANTITATIVE ANALYSE DER CARCINOGENEN WIRKUNG VON DIAETHYLNITROSAMIN. Arzneimittelforschung. 1963 Oct;13:841–851. [PubMed] [Google Scholar]
- Druckrey H., Preussmann R., Ivankovic S., Schmähl D. Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. Z Krebsforsch. 1967;69(2):103–201. [PubMed] [Google Scholar]
- Druckrey H., Schagen B., Ivankovic S. Erzeugung neurogener Malignome durch einmalige Gabe von Athyl-nitrosoharnstoff (ANH) an neugeborene und junge BD IX-Ratten. Z Krebsforsch. 1970;74(2):141–161. [PubMed] [Google Scholar]
- Dulbecco R. Cell transformation by viruses. Science. 1969 Nov 21;166(3908):962–968. doi: 10.1126/science.166.3908.962. [DOI] [PubMed] [Google Scholar]
- HERROLD K. M. EPITHELIAL PAPILLOMAS OF THE NASAL CAVITY; EXPERIMENTAL INDUCTION IN SYRIAN HAMSTERS. Arch Pathol. 1964 Sep;78:189–195. [PubMed] [Google Scholar]
- Heath D. F. The decomposition and toxicity of dialkylnitrosamines in rats. Biochem J. 1962 Oct;85(1):72–91. doi: 10.1042/bj0850072. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ivankovic S., Druckrey H., Preussmann R. Erzeugung neurogener Tumoren bei den Nachkommen nach einmaliger Injektion von Athylnitrosoharnstoff an schwangere Ratten. Naturwissenschaften. 1966 Aug;53(16):410–410. doi: 10.1007/BF00625782. [DOI] [PubMed] [Google Scholar]
- Jasmin G., Cha J. W. Renal adenomas induced in rats by dimethylnitrosamine. An electron microscopic study. Arch Pathol. 1969 Mar;87(3):267–278. [PubMed] [Google Scholar]
- KIDSON C., KIRBY K. S., RALPH R. K. ISOLATION CHARACTERISTICS OF RAPIDLY LABELLED RNA FROM NORMAL RAT LIVER. J Mol Biol. 1963 Sep;7:312–315. doi: 10.1016/s0022-2836(63)80010-8. [DOI] [PubMed] [Google Scholar]
- KIRBY K. S. A new method for the isolation of ribonucleic acids from mammalian tissues. Biochem J. 1956 Nov;64(3):405–408. doi: 10.1042/bj0640405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krüger F. W., Ballweg H., Maier-Borst W. Untersuchungen über die alkylierende Wirkung von 14C-Methylnitrosoharnstoff und 1-14C-Athylnitrosoharnstoff. Experientia. 1968 Jun 15;24(6):592–593. doi: 10.1007/BF02153793. [DOI] [PubMed] [Google Scholar]
- Loveless A. Possible relevance of O-6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature. 1969 Jul 12;223(5202):206–207. doi: 10.1038/223206a0. [DOI] [PubMed] [Google Scholar]
- Ludlum D. B. Alkylated polycytidylic acid templates for RNA polymerase. Biochim Biophys Acta. 1970 Jul 16;213(1):142–148. doi: 10.1016/0005-2787(70)90015-8. [DOI] [PubMed] [Google Scholar]
- Ludlum D. B. The properties of 7-methylguanine-containing templates for ribonucleic acid polymerase. J Biol Chem. 1970 Feb 10;245(3):477–482. [PubMed] [Google Scholar]
- MAGEE P. N., FARBER E. Toxic liver injury and carcinogenesis. Methylation of rat-liver nucleic acids by dimethylnitrosamine in vivo. Biochem J. 1962 Apr;83:114–124. doi: 10.1042/bj0830114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magee P. N., Swann P. F. Nitroso compounds. Br Med Bull. 1969 Sep;25(3):240–244. doi: 10.1093/oxfordjournals.bmb.a070711. [DOI] [PubMed] [Google Scholar]
- Singer B., Fraenkel-Conrat H. Chemical modification of viral ribonucleic acid. 8. The chemical and biological effects of methylating agents and nitrosoguanidine on tobacco mosaic virus. Biochemistry. 1969 Aug;8(8):3266–3269. doi: 10.1021/bi00836a020. [DOI] [PubMed] [Google Scholar]
- Singer B., Fraenkel-Conrat H. Chemical modification of viral ribonucleic acid. VII. The action of methylating agents and nitrosoguanidine on polynucleotides including tobacco mosaic virus ribonucleic acid. Biochemistry. 1969 Aug;8(8):3260–3266. doi: 10.1021/bi00836a019. [DOI] [PubMed] [Google Scholar]
- Swann P. F., Magee P. N. Induction of rat kidney tumours by ethyl methanesulphonate and nervous tissue tumours by methyl methanesulphonate and ethyl methanesulphonate. Nature. 1969 Aug 30;223(5209):947–949. doi: 10.1038/223947a0. [DOI] [PubMed] [Google Scholar]
- Swann P. F., Magee P. N. Nitrosamine-induced carcinogenesis. The alklylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate. Biochem J. 1968 Nov;110(1):39–47. doi: 10.1042/bj1100039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swann P. F. The rate of breakdown of methyl methanesulphonate, dimethyl sulphate and N-methyl-N-nitrosourea in the rat. Biochem J. 1968 Nov;110(1):49–52. doi: 10.1042/bj1100049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Villa-Trevino S., Shull K. H., Farber E. The inhibition of liver ribonucleic acid synthesis by ethionine. J Biol Chem. 1966 Oct 25;241(20):4670–4674. [PubMed] [Google Scholar]