Dose-threshold for thyroid tumor-promoting effects of orally administered kojic acid in rats after initiation with N-bis(2-hydroxypropyl) nitrosamine.
-
- TAMURA Toru
- Division of Pathology, National Institute of Health Sciences
-
- MITSUMORI Kunitoshi
- Division of Pathology, National Institute of Health Sciences Division of Veterinary Pathology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology
-
- ONODERA Hiroshi
- Division of Pathology, National Institute of Health Sciences
-
- FUJIMOTO Nariaki
- Department of Cancer Research, Research Institute of Radiation Biology and Medicine, Hiroshima University
-
- YASUHARA Kazuo
- Division of Pathology, National Institute of Health Sciences
-
- TAKEGAWA Kiyoshi
- Division of Pathology, National Institute of Health Sciences Safety Evaluation Drug Development Laboratories, Pharmaceutical Research Division, WelFide Corporation
-
- TAKAGI Hisayoshi
- Division of Pathology, National Institute of Health Sciences
-
- HIROSE Masao
- Division of Pathology, National Institute of Health Sciences
この論文をさがす
抄録
In order to evaluate the threshold dose of thyroid tumor-promoting effects of KA, male F344 rats were initiated with N-bis(2-hydroxypropyl) nitrosamine (DHPN; 2000 mg/kg body wt., single s.c. injection) and, starting 1 week later, received pulverized basal diet containing 0%, 0.002%, 0.008%, 0.03%, 0.125%, 0.5% or 2%KA for 20 weeks. Five rats each in the 0%, 0.125%, 0.5% and 2%KA groups were sacrificed at week 12, and 10 rats each in all groups at week 20. As an additional experiment, three groups without DHPN initiation received basal diet, a diet containing 0.5% or 2%KA for 20 weeks. The serum T4 levels were significantly decreased in the DHPN-initiated groups given 0.125%KA or more at week 12. No significant decreases in serum T3 levels were observed in the groups treated with DHPN+KA and a significant increase was evident in the 2%KA-alone group at week 20. Some rats in the DHPN+2%KA group at weeks 12 and 20 and the 2%KA-alone group at week 20 showed pronounced elevation of serum TSH. Thyroid weights were significantly increased in the DHPN-initiated groups receiving 0.5% and 2%KA at weeks 12 and 20 and in the 2%KA-alone group at week 20. Histopathologically, the incidences of focal thyroid follicular cell hyperplasias in the DHPN-initiated groups treated with 0.125%, 0.5% and 2%KA at week 20 were 5/10, 10/10 and 8/8 rats, respectively. At week 20, adenomas were observed in 7/10 rats in the DHPN+0.5%KA group and 8/8 rats in the DHPN+2%KA group, and carcinomas were observed in 6/8 rats in the DHPN+2%KA group. In the groups without DHPN initiation, only focal follicular cell hyperplasia was observed in 1/9 rats in the 2%KA-alone group. These results suggest that the no-observed-adverse effect for the thyroid tumor-promoting effect of KA is 0.03% (15.5 mg/kg/day) under the present experimental conditions, and that KA possesses weak tumorigenic activity in rats due to continuous serum TSH stimulation by a non-genotoxic mechanism.
収録刊行物
-
- The Journal of Toxicological Sciences
-
The Journal of Toxicological Sciences 26 (2), 85-94, 2001
一般社団法人 日本毒性学会
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1390001204901817600
-
- NII論文ID
- 110001806907
-
- NII書誌ID
- AN00002808
-
- COI
- 1:CAS:528:DC%2BD3MXlslKhtbk%3D
-
- ISSN
- 18803989
- 03881350
- http://id.crossref.org/issn/10966080
-
- NDL書誌ID
- 5774134
-
- PubMed
- 11429971
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可