Carcinogenesis and mutagenesis by N-nitroso compounds having a basic center.
Two N-nitroso compounds that are derivatives of N,N-dimethylethylenediamine and are therefore strongly basic, were tested for carcinogenic activity. They were methylnitrosamino-N,N-dimethylethylamine (MNDMEA) and N,N-dimethylaminoethylnitrosoethylurea (DMENEU). Each was administered orally to male and female F344 rats by gavage. MNDMEA was also given by gavage to Syrian hamsters and to rats as a solution in drinking water. The response of rats treated with MNDMEA was almost the same by the two modes of treatment and all developed tumors of the esophagus and died in less than 40 weeks; many also had tumors of the nasal mucosa. Hamsters were less susceptible to the nitrosamine than rats, since they survived longer following a larger dose and the tumor incidence was small; several hamsters had tumors of the nasal mucosa, some males also had tumors of the liver and lung and one male and two females had a tumor of the colon. Although it is a strong directly acting mutagen, dimethylaminoethylnitrosoethylurea was weakly carcinogenic in rats, giving rise to tumors of the uterus and mammary gland in females, but having no particular target organ in male rats. The presence of a basic center in these N-nitroso compounds does not prevent their absorption nor their entry into cells, which they can transform to tumors.
Lijinsky
W
W
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702.
Kovatch
R M
RM
Saavedra
J E
JE
D000284:Administration, Oral; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D006224:Cricetinae; D004938:Esophageal Neoplasms / Q000139:chemically induced* / Q000473:pathology; D005021:Ethylamines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D007202:Indicators and Reagents; D008297:Male; D008647:Mesocricetus; D008744:Methylamines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009603:Nitroso Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D002273:Carcinogens; D005021:Ethylamines; D007202:Indicators and Reagents; D008744:Methylamines; D009153:Mutagens; D009603:Nitroso Compounds; D009607:Nitrosourea Compounds; C074123:N,N-dimethylaminoethylnitrosoethylurea; C074122:methylnitrosamino-N,N-dimethylethylamine