ダイオキシン類の発がん性への影響

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タイトル別名
  • Effect of Exposure to Dioxins, as Endocrine Disruptors, on Carcinogenesis
  • ケンキュウ サブグループ 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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PCB126胎生期曝露はN-methyl-N-nitorosourea誘発前立腺発癌を用量依存的に抑制することが明らかとなり,その原因の一つとして前立腺癌細胞におけるAndrogen Receptorの発現抑制が示唆された。PCB126胎生期曝露は雄ラットに対してAndrogen Receptorを介し抗アンドロゲン様に作用することが推定された。

Although polychlorinated biphenyls (PCBs) are fat-soluble environmental pollutants stored breast fatty tissue and secreted in milk, the precise evidence of carcinogenesis from exposure to PCBs remains unclear. The aim of this study was to investigate the dose-response relationship prenatal exposure of 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126) for N-methl-N-nitrosourea (MNU) induced rat prostate carcinogenesis. Male Sprague-Dawley rats whose dams had been injected (i.g.) with 25pg, 2.5ng, 250ng, 7.5μg of PCB126/kg, or the vehicle, on days 13 to 19 post-conception. 12-weeks-old male offsprings were injected (i.v.) with 45 mg MNU/kg. The concentration of PCB126 in the liver of the 12-weeks-old was compared to the vehicle-group, found to be significantly higher in the 7.5μg-group, but other group was nearly to that of the vehicle group. The experiment was terminated when the pups were 75-weeks-old. The 7.5μg, 250ng and 2.5ng-group showed reduction of prostate carcinogenesis, but the 25pg revealed increases incidence of carcinoma that is a similar incidence of the vehicle-group. The present studies indicated that prenatal exposure of high to relatively low dose PCB126 acted as an inhibiting agent toward MNU-induced rat prostate carcinogenesis. This effect partly might be due to an inhibition of androgen receptor (AR) expression at prostate, as relatively low dose PCB126 injected group, such as the 2.5ng group, showed inhibition of AR expression at prostatic lesions.

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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