Journal Article

Promoting effects of xylazine on development of thyroid tumors in rats initiated with <i>N</i>-bis(2-hydroxypropyl)nitrosamine and the mechanism of action

Kazuo Yasuhara, Takatoshi Koujitani, Kiyoshi Takegawa, Masahiro Nasu, Hiroshi Onodera, Hisayoshi Takagi, Masao Hirose and Kunitoshi Mitsumori

in Carcinogenesis

Volume 22, issue 4, pages 613-618
Published in print April 2001 | ISSN: 0143-3334
Published online April 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.4.613
Promoting effects of xylazine on development of thyroid tumors in rats initiated with N-bis(2-hydroxypropyl)nitrosamine and the mechanism of action

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To cast light on whether xylazine hydrochloride (XZ), a veterinary medicine commonly used as a sedative agent for food-producing animals, has any promoting potential for thyroid carcinogenesis, the following studies were performed. In Experiment I, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ for 52 weeks with or without initiation with 2400 mg/kg N-bis(2-hydroxypropyl)nitrosamine (DHPN). Focal follicular cell hyperplasias, adenomas and/or carcinomas were induced in the DHPN alone, XZ alone and DHPN+XZ groups, and the incidences and multiplicities of these lesions in the DHPN+XZ group were significantly increased as compared with the DHPN alone case. In Experiment II, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ and were examined for serum levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) at weeks 1, 2 and 4. In the XZ group, significant increase in thyroid weight and decrease in serum T4 levels were observed at all time points. Serum T3 and TSH levels were significantly decreased and increased, respectively, at week 1, but returned to within the control range thereafter. In Experiment III, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ, they were examined for thyroid iodine uptake and organification of XZ after 1 and 2 weeks. The thyroidal iodine uptake per milligram of thyroid and the amount of iodine bound to 1 mg protein showed a tendency for decrease at week 1 and significant decrease at week 2. These results indicate that XZ has tumor-promoting effects on thyroid follicular cells, and suggest an involvement of alterations in thyroid-related hormone levels due to inhibition of thyroid iodine uptake and organification, resulting, provably, in serum TSH stimulation depending on continuous reduction of serum T4 level through the feedback system in the pituitary–thyroid axis.

Keywords: DHPN, N-bis(2-hydroxypropyl)nitrosamine; DMA, 2,6-dimethylaniline; H-E, hematoxylin and eosin; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; XZ, xylazine hydrochloride.

Journal Article.  4759 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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