Induction of hepatic cytochrome P450 and examination of ovarian steroid receptor homeostatis in three generations of mink consuming PCB-contaminated carp from Saginaw Bay, Lake Huron

The mink population of the Great Lakes basin has been declining over the last six decades. Although part of this decline may be due to increasing use of land previously part of the mink habitat, a larger cause is the contamination of the Great Lakes environment with halogenated aromatic hydrocarbons such as polychlorinated biphenyls, polybrominated biphenyls, polychlorinated dibenzodioxins, and polychlorinated dibenzofurans. Mink were discovered to be extremely sensitive to these contaminants, particularly in terms of their reproductive toxicity. A feeding study was conducted in which adult mink were fed one of three diets containing Saginaw Bay carp to provide 0.25, 0.5, or 1.0 ppm polychlorinated biphenyls. A fourth group of mink was fed a control diet containing ocean fish, which provided 0.0 ppm polychlorinated biphenyls. Mink were bred after 3 months consumption of the diet, and half of the adults and kits were transferred to the control diet at weaning of the kits. The mink were bred again during the following season, after 10 or 13 months on the diets. The animals were sacrificed at weaning of the second generation of kits. In order to determine the potential for a biomarker of halogenated aromatic hydrocarbon consumption in mink, cytochrome P450 enzyme activity was measured in livers of 217 mink which had consumed diets containing Great Lakes fish for up to eighteen months. The activity of cytochrome P450IA1 had a greater dose-response relationship to PCB consumption than did the other cytochrome P450 enzyme activities measured. Hepatic and uterine estrogen receptor concentrations were measured in tissues from the 143 female mink to determine if the reproductive toxicity observed in mink may be due to decreased estrogen receptor concentrations, and thus an inability to detect varying concentrations of estrogen in the blood. In general, the hepatic estrogen receptor concentration decreased in a dose-dependent manner with increasing PCB concentration in the diet. Uterine estrogen receptor concentrations did not change with increasing dietary PCB concentrations. Uterine progesterone receptor concentration was also unaffected.