ダイオキシン類の発がん性への影響

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  • Effect of Exposure to Dioxins, as Endocrine Disruptors, on Carcinogenesis
  • ケンキュウ サブ グループ 5 ダイオキシンルイ ノ ハツガンセイ エ ノ エイキョウ

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比較的低用量PCB126胎生期暴露群のラットでは,DMBA投与後の肝臓におけるCYP1B1mRNA & ProteinとAhR mRNA & Protein発現亢進することが明らかとなった。この結果は,比較的低用量PCB126胎生期暴露群のラットでは,生後50日齢において有意に発がん性の高い体内環境になっていることがmRNA & Proteinレベルでも示唆された。この結果は我々の昨年度の研究成果を支持するものであった。

Previously we reported the finding that prenatal exposure to a relatively low dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a high dose decreased it. One of the most important factors determining the sensitivity to mammary carcinogenesis is the metabolic stage at administration of the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct this metabolism. We investigated the hepatic expression of CYP1 and AhR following oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 ug of PCB 126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1 and AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 ug group) prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and immunhistochemical analyses were consistent with mRNAs changes. Because DMBA oxidation produces a highly mutagenic metabolite and is finally catalyzed by CYP1B1, a relatively low PCB126 dose might produce the biological character to potentially increase the risk of DMBA-induced mammary carcinoma.

麻布大学ハイテク・リサーチ・センター研究プロジェクト 研究サブ・グループ5

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