4.5 Article Proceedings Paper

Reduced levels of 1,25-dihydroxyvitamin D3 in rat dams and offspring after exposure to a reconstituted PCB mixture

Journal

TOXICOLOGICAL SCIENCES
Volume 57, Issue 2, Pages 292-301

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/toxsci/57.2.292

Keywords

polychlorinated biphenyls; vitamin D; development; steroids; rat

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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 darns. 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.

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