Modifying Effects of 2,6-Dimethylaniline on Nasal Carcinogenesis in RasH2 Mice Initiated with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone.

Abstract

In order to investigate the nasal carcinogenic potential and nasal tumor modifying effects of 2,6-dimethylaniline (DMA), a metabolite of xylazine which is used for food-producing animals, male transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) were given diet containing 0 or 2000 ppm DMA for 51 weeks after initiation with/without 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Their non-transgenic CB6F1 littermates (non-Tg mice) were also treated in the same manner. Histopathologically, in rasH2 mice, the incidences of inflammations, respiratory metaplasias of the olfactory epithelium, and hyperplasias of the respiratory epithelium in the NNK+DMA group significantly increased as compared with those in the NNK alone group. In both rasH2 mice and non-Tg mice, proliferative Bowman’s glands were induced in the NNK alone, DMA alone, and NNK+DMA groups. The value for PCNA-positive index of proliferative Bowman’s glands in the NNK+DMA group of rasH2 mice significantly increased as compared with the NNK alone case. In rasH2 mice, the incidence of adenomas (33%) in the NNK+DMA group that might be derived from proliferative Bowman’s glands was slightly, but not significantly, higher than that in the NNK alone group. These results suggest that DMA promotes the development of nasal proliferative lesions in rasH2 mice.