Preliminary Evaluation of Toxicologic and Carcinogenic Risks of Copper Gluconate in Rats Given Multiple Carcinogens
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概要
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The present study was conducted as a preliminary evaluation of toxicologic and carcinogenic risks of copper gluconate and to determine its optimal dose for use in an upcoming study utilizing the medium-term multi-organ carcinogenesis protocol. Male BrlHan:WIST@Jcl (GALAS) rats were initially treated with N-nitrosodiethylamine, N-methylnitrosourea, 1,2-dimethylhydrazine, N-butyl-N-(4-hydroxybutyl)-nitrosamine and 2,2-dihydroxy-di-n-propylnitrosamine for a total multiple initiation period of 4 weeks. In addition, rats were fed a diet containing copper gluconate at 0, 1000, 3000, 4800, 6000, or 12000 ppm from the commencement for 13 weeks. While no systemic toxicity was detected, hepatic granulomas were observed at copper gluconate doses of 6000 ppm, or greater. Hepatic copper accumulation and metallothionein induction were demonstrated at doses of 3000 ppm and 1000 ppm, respectively, or greater. Putative preneoplastic lesions in the liver appeared to increase at a dose of 12000 ppm, and 8-hydroxydeoxyguanosine formation was enhanced at doses of 6000 ppm, or greater. These results suggest that copper gluconate exerts effects on the liver at the relatively low dietary dose of 1000 ppm and causes hepatic injury at 6000 ppm. The hepatotoxicity and possible hepatocarcinogenicity of copper gluconate may be attributable to oxidative stress due to the impairment of hepatic copper metabolism.
- 日本毒性病理学会の論文
- 2006-09-30
著者
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Nakae Dai
東京都健康安全研究センター
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Nakae Dai
Department Of Environmental Health And Toxicology Tokyo Metropolitan Institute Of Public Health:toky
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Nakae Dai
Tokyo Metropolitan Institute Of Public Health
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MAEKAWA Akihiko
Chemical Management Center, National Institute of Technology and Evaluation
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Yoshida Midori
National Institute of Health Sciences
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SUZUKI Noriko
Department of Pathology, Sasaki Institute
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Juneja Lekh
Taiyo Kagaku Co. Ltd.
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Okubo Tsutomu
Taiyo Kagaku Co. Ltd.
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Yoshida Midori
Div. Of Pathology National Inst. Of Health Sciences
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Yoshida Midori
Experimental Pathology National Institute Of Radiological Sciences
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Igarashi Maki
Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate Scho
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Abe Masayoshi
Toxicology and Environmental Science Department, Biological Research Laboratories, Nissan Chemical I
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USUDA Koji
Toxicology and Environmental Science Department, Biological Research Laboratories, Nissan Chemical I
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FURUKAWA Satoshi
Toxicology and Environmental Science Department, Biological Research Laboratories, Nissan Chemical I
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Usuda Koji
Biological Research Laboratories Nissan Chemical Industries Ltd.
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Igarashi Maki
Laboratory Of Protection Of Body Function Department Of Food And Nutritional Science Graduate School
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Abe Masayoshi
Department Of Pathology Sasaki Institute
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Furukawa Satoshi
Biological Research Laboratories, Nissan Chemical Industries, Ltd.
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Abe Masayoshi
Biological Research Laboratories, Nissan Chemical Industries, Ltd.
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Maekawa A
Chemical Management Center National Inst. Of Technol. And Evaluation
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Maekawa Akihiko
Chemical Management Center National Institute Of Technology And Evaluation
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Usuda Koji
Shiraoka Research Station Of Biological Science Nissan Chemical Industries Ltd
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Abe Masayoshi
Biological Research Laboratories Nissan Chemical Industries Ltd.
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Furukawa Satoshi
Biological Research Laboratories Nissan Chemical Industries Ltd.
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Nakae Dai
Department Of Pathology Sasaki Institute
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Suzuki Noriko
Department Of Biochemistry And Molecular Biology Division Of Gene Therapy Research Center For Advanc
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Suzuki Noriko
Department Of Clinical And Molecular Endocrinology Tokyo Medical And Dental University Graduate Scho
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Nakae Dai
Tokyo Metropolitan Inst. Of Public Health
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Furukawa Satoshi
Shiraoka Research Station Of Biological Science Nissan Chemical Industries Ltd
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JUNEJA LEKH
Taiyo Kagaku Co., Ltd.
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Suzuki Noriko
Department of Applied Pharmacology, Kyoto Pharmaceutical University
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