HORMONAL DISREGULATION MECHANISM IN THE RAT THYROID TUMOR INDUCED BY DINICONAZOLE
スポンサーリンク
概要
- 論文の詳細を見る
To assess the toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diniconazole, (E)-1-(2,4-dichlorophenyl)-4, 4-dimethyl-2-(1, 2, 4-triazol-1-yl)-1-penten-3-ol, a 3-month subacute feeding study was conducted in male Crj: CD (SD) rats by administering diniconazole in diet at concentrations of 0, 100, 1,000, or 2,000 ppm. Examinations mainly for thyroid functions were performed at Weeks 2, 4 and 13. Measurement of serum hormone levels revealed continuous decreases in serum thyroxine (T_4) and free T_4 levels at and above 1,00 ppm and increase in serum thyroid stimulating hormone (TSH) level at 2,000 ppm concurrently with liver weight and hepatic UDP-glucuronyltransferase (UDP-GT) increases at and above 1,000 ppm. No changes were observed in serum triiodothyronine (T_3) and free T_3 levels. Increase in thyroid uptake of ^<125>I and organification of ^<125>I in the thyroid at 2,000 ppm and thyroid follicular cell hyperplasia at and above 1,000 ppm were also observed. However, no compound-related changes were observed in autopsy and organ weight in the thyroid. Based on the above results, diniconazole induces increases in the hepatic UDP-GT activity and the thyroid hormone excretion from the liver. The increased excretion of thyroid hormones causes decrease in serum T_4 and free T_4 levels, triggering the feedback mechanism of the pituitary gland, promotion of TSH release from the pituitary gland and increase in serum TSH level. The increased serum TSH level probably leads to increased ^<125>I uptake of thyroid and thyroid follicular cell hyperplasia. Thus, the thyroid tumorigenesis in rats treated with diniconazole is due to the secondary overstimulant effect on the thyroid by increased serum TSH level. The toxicological significance in humans is extremely low and it is unlikely that diniconazole would increase thyroid tumor in humans even if diniconazole were to alter normal thyroid hormone level in humans.
- 日本トキシコロジー学会の論文
- 1993-02-25
著者
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YAMADA Tomoya
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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SEKI Takaki
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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Seki Takaki
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Sukata Tokuo
Environmental Health Science Lab. Sumitomo Chemical Co. Ltd.
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MATSUO Masatoshi
Environmental Health Science Lab., Sumitomo Chemical Co., Ltd.
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Matsuo Masatoshi
Cooperative Research Center For Advanced Science And Technology Osaka University
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細川 暁
Drug Safety & Disposition Research Laboratories Eisai Co. Ltd.
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Ito S
Yamanouchi Pharmaceutical Co. Ltd. Tokyo Jpn
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Yamada T
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Yoshioka Kaoru
Environmental Health Science Laboratory Sumitomo Chemical Company Ltd.
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Yamada H
Faculty Of Pharmaceutical Sciences Kyushu University
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HOSOKAWA Shunji
Environmental Health Science Laboratory, Sumitomo Chemical Co., LTD.
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Hosokawa S
Drug Safety & Disposition Research Laboratories Eisai Co. Ltd.
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Hosokawa Shunji
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Yanai T
United Graduate School Of Veterinary Sciences Gifu University
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Nakamura J
Laboratory Of Animal Ecology Department Of Ecology And Systematics Graduate School Of Agriculture Ho
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NAKAMURA Jun
Environmental Health Science Lab., Sumitomo Chemical Co., Ltd.
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ITO Seiichi
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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MURAKAMI Masakazu
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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INEYAMA Mariko
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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YAMADA Hirohiko
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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Ineyama Mariko
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Murakami M
Univ. Tokyo Tokyo
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Seki Takaki
Environmental Health Science Laboratory Sumitomo Chem. Co. Ltd.
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