open access

https://hdl.handle.net/2115/79723

環境化学物質への曝露に関するネコのシトクロムP450の毒性学的研究 [全文の要約]

英語

PCBs

2020-09-25

Hokkaido University

https://www.lib.hokudai.ac.jp/dissertations/copy-guides/

Cats have been known to be extremely sensitive to chemical exposures. The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. However, the characterization of cytochrome P450 (CYP), the dominant enzyme in phase I metabolism, in cats has not extensively been studied. In addition, the information regarding the organohalogens-induced CYP expression in cats is limited. I aimed to elucidate the mRNA expression of the CYP1–CYP3 families in the cat tissues and to investigate the CYP mRNA expression related to PCBs and BDE-209 exposures. In cats, the greatest abundance of CYP1–CYP3 was expressed in the liver, but some extrahepatic isozymes were found in the kidney (CYP1A1), heart (CYP1B1), lung (CYP2B11 and CYP2S1) and small intestine (CYP3A131). In cats, CYP1A1, CYP1A2 and CYP1B1 were significantly upregulated in the liver as well as in several tissues exposed to PCBs, indicating that these CYPs were distinctly induced by PCBs. The strong correlations between 3,3’,4,4’-tetrachlorobiphenyl (CB77) and CYP1A1 and CYP1B1 mRNA expressions were noted, demonstrating that CB77 could be a potent CYP1 inducer. All selected CYP isoforms showed no significant difference in mRNA expressions between control and BDE-209 exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the BDE-209 exposure group compared to control group. The present results indicate that the acute exposure of PCBs could clearly upregulate CYP1 family, while chronic exposure of BDE-209 could not alter CYP expression in the liver of cats.

甲第14271号

博士(獣医学)

(主査) 教授 石塚 真由美, 教授 滝口 満喜, 准教授 池中 良徳, 准教授 水川 葉月（愛媛大学）

獣医学研究科（獣医学専攻）

博士論文

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