Skin tumors induced by painting nitrosoalkylureas on mouse skin

The carcinogenic action of nitrosamides has been investigated by applying a 0.04 M solution in acetone of 17 nitrosoalkylureas and one nitrosoalkylcarbamate to the shaved interscapular skin of female Swiss mice. Each of a group of 20 mice received 25 microliter of solution twice a week for 40 or 50 weeks, after which the animals were observed until death or 100 weeks. The appearance and progression of skin tumors within the painted area was charted for each animal. Nitroso-2-fluoroethylurea was toxic to the skin and was retested using a 0.01 M solution in acetone. No tumors was seen with nitrosoallylurea, nitroso-iso-butylurea, nitrosobenzylurea, and nitroso-2-phenylethylurea. The most potent compounds were nitrosomethylurea, nitrosoethylurea, and nitroso-2-fluoroethylurea. Nitroso-n-amylurea and nitroso-n-hexylurea were somewhat less potent, each inducing tumors in 11 of 20 mice. Nitrosocarbaryl gave rise to skin tumors in eight mice. The remaining compounds, nitroso-n-propylurea, nitroso-iso-propylurea, nitroso-n-butylurea, nictroso-sec-butylurea, nitroso-n-undecylurea, nitroso-n-tridecylurea, nitrosophenylurea, and nitrosocyclohexylurea were much less effective skin carcinogens, yielding tumors in from one to five mice. No good correlation was apparent between the relative stability of the compounds, their mutagenicity to Salmonella and their carcinogenicity to mouse skin.