TIME COURSE OBSERVATION OF THYROID PROLIFERATIVE LESIONS AND SERUM LEVELS OF RELATED HORMONES IN RATS TREATED WITH KOJIC ACID AFTER DHPN INITIATION

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概要

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• Time course changes in thyroid proliferative lesions as well as related hormone levels in the blood of male F344 rats given N-bis (2-hydroxypropyl) nitrosamine (DHPN: 2800 mg/kg body weight, single s.c. injection) as an initiation treatment followed by pulverized basal diet containing 0% (Group 2), 2% (Group 3) or 4% (Group 4) kojic acid (KA) were examined at Weeks 1, 2, 4, 8 and 12. As an untreated control group (Group 1), rats were given basal diet for 13 weeks and examined in the same manner. Serum T3/T4 levels in the DHPN+2% KA and DHPN+4% KA groups were significantly reduced as compared with the DHPN-alone group at each time point. Serum TSH levels in both DHPN+KA groups were significantly increased at each time point in a treatment period-dependent manner from Weeks 1 to 12, and the extent of elevation was more remarkable in the DHPN+4% KA group. At Week 2, there were no statistically significant intergroup differences in liver T4-UDP-GT activities on a milligram microsomal protein basis. Histopathologically, no thyroid proliferative lesions were observed in the untreated control group or the DHPN-alone group. However, diffuse follicular cell hypertrophy and decreased colloid in the thyroid were apparent in all rats of the DHPN+KA groups at each time point. In addition, local follicular cell hyperplasias and adenomas of the thyroid were observed at high incidence in the DHPN+2% KA group from Week 4 and in the DHPN+4% KA group from Week 8. Multiplicities of focal follicular cell hyperplasias and adenomas of the thyroid in the DHPN+2% KA group were significantly greater than those in the DHPN+4% KA group at Week 8. In the pituitary, an increase in the number of TSH producing cells with expanded cytoplasm was apparent from Weeks 4 to 12 in both DHPN+KA groups. These results strongly suggest that thyroid proliferative lesions were induced by KA administration due to continuous serum TSH stimulation through the negative feedback mechanism of the pituitary-thyroid axis, resulting from depression of serum T3 and T4.

• 日本トキシコロジー学会の論文
• 1999-08-17

著者

• Hirose Masao

  Division of Pathology, National Institute of Health Sciences

• 高橋 通正

  (独)産業技術総合研究所 環境管理技術研究部門

• ONODERA Hiroshi

  Division of Pathology, National Institute of Health Sciences

• Yasuhara Kazuo

  Divisions Of Toxicology National Institute Of Hygienic Sciences

• Yasuhara Kazuo

  Division Of Pathology National Institute Of Health Sciences

• TAKAGI Hisayoshi

  Division of Pathology, National Institute of Health Sciences

• TAMURA Toru

  Division of Pathology, National Institute of Health Sciences

• MITSUMORI Kunitoshi

  Division of Pathology, National Institute of Health Sciences

• Takizawa Tamotsu

  Division Of Pathology National Institute Of Health Sciences

• Takegawa Kiyoshi

  Division of Pathology, National Institute of Health Sciences

• Tamura Toru

  Division Of Pathology National Institute Of Health Sciences

• Takagi Hisayoshi

  国立医薬品食品衛生研究所

• Takagi Hisayoshi

  Division Of Pathology National Institute Of Health Sciences

• Onodera Hiroshi

  東京都健康安全研究センター

• Onodera Hiroshi

  Pharmaceuticals And Medical Devices Agency

• Tamura Tomohide

  Medical Oncology Division National Cancer Center Hospital

• Takegawa K

  Division Of Pathology National Institute Of Health Sciences:safety Evaluation Drug Development Labor

• Takegawa Kiyoshi

  三菱ウェルファーマ

• Takada Koichi

  Safety Evaluation Laboratory Yoshitomi Pharmaceutical Industries Co. Ltd.

• Takegawa K

  Toxicology Laboratories Pharmaceutical Research Division Mitsubishi Pharma Corporation

• Takegawa Kiyoshi

  Department Of Pathology National Institute Of Health Sciences

• Takegawa Kiyoshi

  Safety Evaluation Drug Development Laboratories Pharmaceutical Research Division Yoshitomi Pharmaceu

• Takahashi M

  National Inst. Health Sci. Tokyo

• Kitamura Y

  Division Of Pathology National Institute Of Health Sciences

• Takada Koichi

  国立医薬品食品衛生研究所

• Hirose Masao

  Division Of Pathology National Institute Of Health Sciences

• Mitsumori Kunitoshi

  Division Of Pathology National Institute Of Health Sciences

• TAKAHASHI Masakazu

  Department of Pathology, Sasaki Institute

• Funakoshi Takushi

  Pharmaceutical Research Division, Kyushu Laboratories, Yoshitomi Pharmaceutical Industries, Ltd.

• Takada Koichi

  Division Of Toxicology Biological Safety Research Center National Institute Of Health Sciences

• Takada Koichi

  Dept. Of Toxicology Bioological Safety Research Center National Institute Of Hygienic Sciences

• Funakoshi Takushi

  Pharmaceutical Research Division Kyushu Laboratories Yoshitomi Pharmaceutical Industries Ltd.

• Onodera H

  Pharmaceuticals And Medical Devices Agency

• Takada Kouichi

  Division Of Toxicology Biological Safety Research Center National Institute Of Health Sciences

• Takahashi Masakazu

  Department Of Microbiology Niigata College Of Pharmacy

• Matsumoto K

  Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology

• Takada Koichi

  Divisions Of Toxicology National Institute Of Hygienic Sciences

• Yasuhara Kazuo

  Division Of Medicinal Chemistry And Pharmacognosy Ohio State University

• Takada Koichi

  Division Of Toxicology Biological Safety Research Center National Institute Of Hygienic Sciences

• Takada Koichi

  吉富製薬福崎安全性研究所

• Takahashi Masakazu

  Department Of Food Science And Technology Faculty Of Agriculture Kyoto University

• Tamura Toru

  Division Of Pathology National Institute Of Health

• Takahashi Masakazu

  Department Of Bioscience Faculty Of Biotechnology Fukui Prefectural University

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