Molecular localization of copper and zinc in rat fetal liver in dietary and drug-induced copper deficiency.
The teratogenicity of copper deficiency is well known, but underlying mechanisms have not been delineated. One method of studying the biochemical lesions of copper deficiency is the use of chelating drugs with different chemical characteristics. The teratogenicity of a copper deficient diet and of diets containing either D-penicillamine or triethylenetetramine is quite different, although all three diets result in decreased fetal liver copper levels. Feeding D-penicillamine can result in decreased fetal liver zinc, while feeding triethylenetetramine can result in increased fetal liver zinc. The effect of these three diets on fetal liver copper and zinc molecular localization was determined. Gel filtration showed that fetal liver copper and zinc in controls was localized in 3 fractions with MWs of greater than 50,000 (H), 30,000 (I) and 8-10,000 (L). Independent of dietary treatment, as liver copper diminished, copper was missing first from the L peak, then the I peak and with severe deficiency, from the H peak. Drug induced increases and decreases in fetal liver zinc were reflected in the L peak. These data suggest that the absolute levels of copper in the liver of the term fetus determines the distribution of the element among its binding ligands.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002850:Chromatography, Gel; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D005029:Ethylenediamines / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008668:Metallothionein / Q000378:metabolism; D010396:Penicillamine / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D014266:Trientine / Q000633:toxicity*; D015032:Zinc / Q000378:metabolism*
D005029:Ethylenediamines; D003300:Copper; D008668:Metallothionein; D013482:Superoxide Dismutase; D010396:Penicillamine; D015032:Zinc; D014266:Trientine