N-
Nitrosocimetidine (NCM) is a nitrosation product of
cimetidine, a commonly-prescribed
pharmaceutical agent. In spite of its known genotoxicity, NCM has failed to cause
tumors in assays with rats and mice, but has given indications of enhancing or suppressive effects on
tumor development. This possibility was tested by administering NCM topically to the skin or in the
drinking water to mice in which
tumors had been initiated by treatment with chemical
carcinogens. Sencar mouse skin
papillomas initiated by
7,12-dimethylbenzanthracene (DMBA) and promoted by 12-O-decanoylphorbol-13-acetate (TPA), progressed more rapidly to
carcinoma on mice given treatment during stage 3 (after TPA) with NCM (1 mg/week) or
N-methyl-N'-nitro-N-nitrosoguanidine (
MNNG, 120 micrograms/week) [corrected] than on stage 3
acetone controls. Oral NCM (1 g/l
drinking water) did not have this effect but rather suppressed development of
keratoacanthomas, as did stage 3
MNNG or TPA. Primary lung
tumors initiated in BALB/c mice by i.p. injection of
urethane; and
tumors of forestomach, lung, mammary, lymphoid and skin tissues caused in (C57BL/6 X DBA/2)F1 mice by oral DMBA were not markedly affected by NCM given in
drinking water (1000-1800 ppm) until 14-16 months of age. These results confirm NCM's general lack of activity as an in vivo toxicant, but show that under certain circumstances it may enhance or suppress
tumor development.