Carcinogenesis in rats by nitrosodialkylureas containing methyl and ethyl groups given by gavage and in drinking water.
The carcinogenic effects in male and female F344 rats of four nitrosodialkylureas containing methyl or ethyl groups have been compared by two modes of administration, gavage in oil solution or dissolved in drinking water. Weekly doses of 20 and 40 mumol were given to each rat by either route and treatment lasted usually 30 wk, resulting in a total dose per rat of 0.6 or 1.2 mmol. Nitrosodimethylurea and nitroso-1-methyl-3-ethylurea gave rise primarily to tumors of the nervous system, whereas nitrosodiethylurea and nitroso-1-ethyl-3-methylurea gave rise to tumors of the mammary gland, lung, intestinal tract, nervous system, and testicular mesotheliomas. The effect of nitrosodimethylurea was weaker than that of the other three compounds, as measured by rate of mortality with tumors. Drinking water treatment was less effective than treatment by gavage, by the same criterion. The tumorigenic effects paralleled those of the corresponding monoalkylnitrosourea, suggesting the presence in the target organs of receptors for which ethylnitrosoureas or methylnitrosoureas, respectively, have affinity.
Lijinsky
W
W
BRI-Basic Research Program, NCI-Frederick Cancer Research Facility, Maryland 21701.
Saavedra
J E
JE
Kovatch
R M
RM
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens; D004326:Drinking; D005038:Ethylnitrosourea / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D008297:Male; D008770:Methylnitrosourea / Q000031:analogs & derivatives* / Q000633:toxicity; D009420:Nervous System / Q000187:drug effects; D009423:Nervous System Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; C001049:N,N'-dimethylnitrosourea; C061090:1,3-diethyl-1-nitrosourea; D008770:Methylnitrosourea; C061087:1-nitroso-1-methyl-3-ethylurea; C061089:1-nitroso-1-ethyl-3-methylurea; D005038:Ethylnitrosourea