Lilienthal H, Fastabend A, Hany J, Kaya H, Roth-Härer A, Dunemann L, Winneke G
Departments of Neurobehavioral Toxicology and Analytical Chemistry, Medical Institute of Environmental Hygiene, Auf'm Hennekamp 50, D-404225 Düsseldorf, Germany.
Toxicol Sci. 2000 Oct;57(2):292-301. doi: 10.1093/toxsci/57.2.292.
Previous studies revealed effects of polychlorinated biphenyls (PCBs) and other polyhalogenated hydrocarbons on steroid hormone levels and hormone-dependent functions including behavior. In the present study serum concentrations of the vitamin D(3) metabolites 25-hydroxycholecalciferol (25-D) and 1,25-dihydroxycholecalciferol (1,25-D) were determined in rat dams and offspring after exposure to a PCB mixture that was reconstituted according to the congener pattern found in human breast milk. Unmated females were exposed to diets adulterated with 0; 5; 20; or 40 mg PCBs/kg diet. Exposure started 50 days prior to mating and was terminated at birth. Gestational exposure reduced serum concentrations of 1,25-D in dams in a dose-dependent manner. Concentration of 25-D was also decreased at the time of delivery, but not at weaning. Determination of 1,25-D in offspring at weaning revealed reductions in both high-exposure groups. Levels of 25-D were diminished only at the highest exposure level. Internal PCB concentrations in adipose tissue and brains exhibited a linear relation to dosages in diet. Concentrations of PCBs in brains were similar in dams and offspring at birth, but decreased at the end of lactation in dams. In offspring, values increased during this period because of continued exposure via the milk. In the adipose tissue, PCB levels were much lower in offspring than in dams. To our knowledge, this is the first report of PCB-induced effects on vitamin D(3) metabolites. In dams, reductions were seen even at the lowest exposure level used. Further studies are needed to evaluate the biological significance of these reductions in pregnant dams and possible consequences for the developing offspring.
以往的研究揭示了多氯联苯（PCBs）和其他多卤代烃对类固醇激素水平以及包括行为在内的激素依赖性功能的影响。在本研究中，对暴露于一种根据人母乳中同系物模式重构的多氯联苯混合物后的大鼠母鼠及其后代，测定了维生素D(3)代谢产物25-羟基胆钙化醇（25-D）和1,25-二羟基胆钙化醇（1,25-D）的血清浓度。未交配的雌性大鼠被给予掺有0；5；20；或40毫克多氯联苯/千克饲料的日粮。暴露在交配前50天开始，并在出生时终止。孕期暴露以剂量依赖的方式降低了母鼠血清中1,25-D的浓度。分娩时25-D的浓度也有所下降，但断奶时没有。对断奶后代的1,25-D测定显示，两个高暴露组均有降低。仅在最高暴露水平下，2,5-D的水平才有所降低。脂肪组织和大脑中的多氯联苯内部浓度与日粮中的剂量呈线性关系。出生时母鼠和后代大脑中的多氯联苯浓度相似，但母鼠在哺乳期结束时浓度下降。在后代中，由于通过乳汁持续暴露，在此期间该值有所增加。在脂肪组织中，后代的多氯联苯水平远低于母鼠。据我们所知，这是多氯联苯对维生素D(3)代谢产物影响的首次报告。在母鼠中，即使在使用的最低暴露水平下也观察到了降低。需要进一步研究来评估这些在怀孕母鼠中降低的生物学意义以及对发育中后代可能产生的后果。
