| Co-Investigator(Kenkyū-buntansha) |
三科 潤 東京女子医科大学, 医学部, 助教授 (60277192)
MURA Tetsuo Tokyo Woman's Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80093631)
神崎 晋 鳥取大学, 医学部, 教授 (90224873)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The aim of this study was to assess the potency of the biological action of dioxins via lactation on the gene expression in neonates. Maternal rats were treated with a single dose of 50 or 100 mmol/kg 1, 2, 3, 4 - tetrachlorodibenzo-p-dioxin (1, 2, 3, 4 - TCDD), a low potent congener of dioxins, on the first day postpartum (day 1). Induction of CYP1A1 mRNA and other CYP isoenzymes mRNA was quantitatively analyzed by the competitive RT-PCR method. To assess the response to dioxin-induced oxidative stress in neonates via lactation, mRNA expression of the key antioxidant enzymes (AOEs) ; such as ph-GPx, cell-GPx, CuZn-SOD, Mn-SOD and catalse (CAT), were also determined.
The mRNA ratios of CYP 1A1 to β-actin in neonates were dose-dependently increased by the treatment of 1, 2, 3, 4 - TCDD of their mothers. The effect was at its peak on day 6 and sustained at the same level on day 10. Increases of the ratio with 100 mmol/kg 1, 2, 3, 4 ? TCDD on day 2, 6, and 10 were 26-, 40-, and 40-fold of the appropriate controls, respectively. Quantitative analysis of AOEs mRNA showed that ph-GPx and cell-GPx mRNA as well as CuZn-SOD and CAT mRNA in the neonatal liver were suppressed on day2 and returned to the control levels on d 6 and thereafter increased higher than the controls on d 10.
Although the dose of 1, 2, 3, 4 - TCDD selected in this study was about 5000 times higher than the daily intake of dioxins in breast-fed infants, CYP1A1 mRNA was highly induced for a longer period of time than the treated maternal rats. AOE mRNA in the neonatal liver was suppressed only on day 2, probably reflecting increase of lipid peroxidation. Dioxin itself and induced oxidative stress by lactational transfer alters CYP gene expression and may affect the physiological response to oxidative stress.
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