Tumor-promoting activity of 2,6-dimethylaniline in a two-stage nasal carcinogenesis model in N-bis(2-hydroxypropyl)nitrosamine-treated rats.
The potential promotion activity on nasal carcinogenesis of 2,6-dimethylaniline (DMA), an alpha2-adrenergic agonist metabolite of xylazine which is used for food-producing animals as a sedative agent, was examined. Male F344 rats received diet containing 0 or 3000 ppm DMA for 52 weeks after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Histopathological assessment showed the incidence of carcinomas in the DHPN+DMA group (33%) to be significantly elevated as compared with that for the DHPN-alone group (5%). Incidences and/or multiplicity of epithelial hyperplasias and dysplastic foci were also increased in the DHPN+DMA group. These lesions were exclusively observed in the olfactory mucosa. The lowest plasma levels of DMA in tumor- and dysplastic foci-bearing rats were 0.05 and 0.20 microg/ml, respectively. These results indicate that DHPN acts as an appropriate initiator for nasal carcinogenesis and that DMA exerts a tumor-promoting effect on the olfactory mucosa in the rat nasal cavity.
Koujitani
T
T
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
Yasuhara
K
K
Kobayashi
H
H
Shimada
A
A
Onodera
H
H
Takagi
H
H
Hirose
M
M
Mitsumori
K
K
D000236:Adenoma / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000814:Aniline Compounds / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity*; D002277:Carcinoma / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D004357:Drug Synergism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; D009602:Nitrosamines / Q000633:toxicity*; D009669:Nose Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D014420:Turbinates / Q000187:drug effects / Q000473:pathology
D000316:Adrenergic alpha-Agonists; D000814:Aniline Compounds; D002273:Carcinogens; D009602:Nitrosamines; C007766:2,6-xylidine; C012457:diisopropanolnitrosamine