Absence of Tumor Promoting Activity of Xylazine in a Two-stage Nasal Carcinogenesis Model in N-bis(2-hydroxypropyl)nitrosamine-treated Rats

概要

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Potential promotion activity of nasal carcinogenesis by xylazine, an agent commonly used in veterinary medicine as an α2-adrenergic agonist, was examined using a N-bis(2-hydroxypropyl)nitrosamine (DHPN)-initiated two-stage nasal carcinogenesis model. Male F344 rats received diet containing 1,000 (maximum tolerated dose) or 0 ppm xylazine hydrochloride (XZ) for 52 weeks with or without prior a single subcutaneous injection of 2,400 mg/kg of DHPN as an initiation treatment. Histopathologically, epithelial hyperplasias, dysplastic foci, adenomas, undifferentiated carcinomas, and/or a squamous cell carcinoma in the nasal cavity were observed in the groups initiated with DHPN, but the incidences of these proliferative lesions were not altered by the treatment of XZ. Plasma levels of xylazine and 2, 6-dimethylaniline (DMA), a major metabolite and a known nasal promoter/carcinogen were at or below the detection limit (0.02 μg/ml) except in 2 animals of the DHPN + XZ group (DMA concentrations were 0.04 and 0.06 μg/ml). These results suggest that XZ does not have any tumor promoting effect in the nasal tissues and its conversion to carcinogenic DMA is very low in vivo. The possibility of nasal carcinogenic effects of DMA in consumers via ingestion of edible tissues in food-producing animals treated with xylazine is extremely low.
日本毒性病理学会の論文
1999-06-01