Nitrosamine-induced carcinogenesis. The alkylation of N-7 of guanine of nucleic acids of the rat by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate.
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.
D000473:Alkanes; D000478:Alkylation; D000818:Animals; D001923:Brain Chemistry; D002247:Carbon Isotopes; D002273:Carcinogens; D002852:Chromatography, Ion Exchange; D004247:DNA / Q000032:analysis; D005260:Female; D006147:Guanine; D007422:Intestines / Q000032:analysis; D007668:Kidney / Q000032:analysis; D007680:Kidney Neoplasms / Q000139:chemically induced; D008099:Liver / Q000032:analysis; D008168:Lung / Q000032:analysis; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines; D009603:Nitroso Compounds; D009607:Nitrosourea Compounds; D009696:Nucleic Acids; D012313:RNA / Q000032:analysis; D051381:Rats; D013451:Sulfonic Acids; D014508:Urea
D000473:Alkanes; D002247:Carbon Isotopes; D002273:Carcinogens; D009602:Nitrosamines; D009603:Nitroso Compounds; D009607:Nitrosourea Compounds; D009696:Nucleic Acids; D013451:Sulfonic Acids; D006147:Guanine; D012313:RNA; D014508:Urea; D004247:DNA