Honma Takeshi, Suda Megumi, Miyagawa Muneyuki, Wang Rui-Sheng, Kobayashi Kenichi, Sekiguchi Soichiro
Department of Health Effects Research, National Institute of Occupational Safety and Health, Tama-ku, Kawasaki, Japan.
Ind Health. 2009 Jan;47(1):11-21. doi: 10.2486/indhealth.47.11.
PCB153 (2,2',4,4',5,5'-hexachlorobiphenyl), a non-coplanar PCB and the congener most widely distributed in the environment, was orally administered to pregnant Sprague-Dawley (Crj: CD (SD) IGS) rats from gestation day 10 through 16 at doses of 0 (control), 16 and 64 mg/kg body weight. Female pups were sacrificed at 1, 3, 6, and 9 wk, and at 1 yr of age to evaluate the differences in brain neurotransmitters and their metabolites between PCB153-exposed and control groups. Brain levels of norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), acetylcholine (ACh), and choline (Ch) in discrete brain regions or in whole brain were measured. At 1 to 3 wk after birth, brain levels of DA, DOPAC, HVA, 5HT and 5HIAA in PCB-exposed groups were higher than those of the control group. At 9 wk after birth, DA turnover was reduced in half of the four brain areas examined (forebrain and hindbrain), and 5HIAA levels were increased in all brain areas in the PCB-treated group compared to those of the control group. At 1 yr after birth, the levels of DA, DOPAC, and HVA in the hippocampus, hypothalamus, and medulla oblongata were lower in the PCB-exposed groups than in the control group. Prenatal exposure to PCB153 stimulated the turnover of 5HT neurons in the brain of female offspring at early stages (1 to 9 wk) of development. On the other hand, the turnover of DA neurons in the PCB-exposed groups was reduced in late stages (9 wk to 1 yr) of development compared with that of the control group. The brain neurotransmitters of dams treated with PCB were assayed at 3 wk after delivery (15 wk old), and decreases in DA, DOPAC, and HVA were observed. PCB153 reduced the activity of DA neurons in the brain of dams. These results are discussed in relation to health effects observed in humans exposed to PCBs.
多氯联苯153（2,2',4,4',5,5'-六氯联苯）是一种非共平面多氯联苯，也是环境中分布最广泛的同系物，在妊娠第10天至16天，以0（对照）、16和64毫克/千克体重的剂量对怀孕的斯普拉格-道利（Crj:CD(SD)IGS）大鼠进行口服给药。在雌性幼崽1、3、6和9周龄以及1岁时处死，以评估多氯联苯153暴露组和对照组之间脑神经递质及其代谢物的差异。测量离散脑区或全脑中去甲肾上腺素（NE）、3-甲氧基-4-羟基苯乙二醇（MHPG）、多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）、高香草酸（HVA）、5-羟色胺（5HT）、5-羟基吲哚乙酸（5HIAA）、乙酰胆碱（ACh）和胆碱（Ch）的脑水平。出生后1至3周，多氯联苯暴露组的脑内DA、DOPAC、HVA、5HT和5HIAA水平高于对照组。出生后9周，在所检查的四个脑区（前脑和后脑）中的一半，DA周转率降低，与对照组相比，多氯联苯处理组所有脑区的5HIAA水平升高。出生后1年，多氯联苯暴露组海马体、下丘脑和延髓中的DA、DOPAC和HVA水平低于对照组。产前暴露于多氯联苯153会在发育早期（1至9周）刺激雌性后代脑中5HT神经元的周转率。另一方面，与对照组相比，多氯联苯暴露组的DA神经元周转率在发育后期（9周龄至1岁）降低。在分娩后3周（15周龄）对用多氯联苯处理的母鼠的脑神经递质进行了测定，观察到DA、DOPAC和HVA减少。多氯联苯153降低了母鼠脑中DA神经元的活性。结合在接触多氯联苯的人类中观察到的健康影响对这些结果进行了讨论。
