Toxicity and its mechanism of dioxin-like chemicals in infants through their mothers exposed during a pregnancy and lactational period.

本研究的目的是评估二恶英通过哺乳对新生儿基因表达的生物学作用的效力。母鼠在产后第1天(第1天)单次给药1，2，3，4-四氯二苯并-对二恶英(1，2，3，4-TCDD)，剂量为50或100 mmol/kg。用竞争性RT-PCR方法定量分析细胞色素P1A1和其他细胞色素P450同工酶基因的表达。为评价新生儿对二恶英所致的哺乳期氧化应激的反应，本研究还测定了新生儿体内关键抗氧化酶(Ph-GPx、CELL-GPx、CuZN-SOD、Mn-SOD和CAT)的基因表达。母亲给予1，2，3，4-β-TCDD后，新生儿CyP1A1/CuZN-肌动蛋白的mR NA比例呈剂量依赖性增加。作用在第6天达到高峰，第10天维持在同一水平，1、2、3、4、100 mmol/kg1、2、3、4？第2天、第6天和第10天的TCDD分别是相应对照组的26、40和40倍。AOES信使核糖核酸定量分析显示，新生大鼠肝组织中pH-GPX、CELL-GPX、CuZN-SOD和CAT的mRNA在第2天受到抑制，第6天恢复到对照水平，第10天高于对照组。虽然本研究选用的1，2，3，4-TCDD剂量比母乳喂养的婴儿每天摄入二恶英的剂量高约5000倍，但在更长的时间内，CYP1A1 mRNA被高度诱导。新生大鼠肝脏AOE mRNA仅在第2天受到抑制，可能反映了脂质过氧化作用的增强。二恶英本身和通过哺乳转移诱导的氧化应激改变了CYP基因的表达，并可能影响对氧化应激的生理反应。

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.