The anomalous biological activity of nitroso-2-oxopropyl compounds.
The carcinogenic action of a set of N-nitroso compounds containing the 2-oxopropyl group was considered in relation to their metabolism and their activity as alkylating agents for DNA. In contrast with the great carcinogenic potency of methylnitrosourea and ethylnitrosourea, comparable with the corresponding dialkylnitrosamines, 2-oxopropylnitrosourea is a weak carcinogen with a limited range of target organs in rats and hamsters. 2-Oxopropylnitrosochloroethylurea was somewhat weaker than 2-oxopropylnitrosourea and similarly induced spleen hemangiosarcomas in hamsters, but few tumors of any kind in rats. The relatively much more potent carcinogenicity of nitrosobis-(2-oxopropyl)amine, nitroso-(2-hydroxypropyl) (2-oxopropyl) amine and methylnitroso-2-oxopropylamine suggests that the activity of an oxopropylating agent is not involved in carcinogenesis by nitroso-2-oxopropylamines. The nitrosamines are likely to undergo extensive metabolism to form proximate carcinogenic moieties, probably including the methyldiazonium ion, which are responsible for the induction of a broad range of tumors in rats and hamsters. These include tumors of the liver, pancreas ducts, lung and nasal mucosa in hamsters, and esophagus, liver, lung, thyroid, kidney, trachea, bladder and nasal mucosa in rats.
Lijinsky
W
W
Laboratory of Chemical and Physical Carcinogenesis, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, MD 21701.
D000818:Animals; D006224:Cricetinae; D007659:Ketones / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009603:Nitroso Compounds / Q000633:toxicity*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D007659:Ketones; D009603:Nitroso Compounds; D009607:Nitrosourea Compounds; D011437:Propylamines