Lindane embryotoxicity and differential alteration of cysteine and glutathione levels in rat embryos and visceral yolk sacs.
The lindane embryotoxicity and associated changes in cysteine (CYS) and glutathione (GSH) status have been investigated in the early organogenesis-stage rat conceptus utilizing whole embryo culture techniques. Direct exposure of gestational day 10 (GD 10) conceptuses to lindane (50, 100, 200, 300, and 400 microM) in the culture medium resulted in a dose- and time-dependent increase in mortality (88% at 400 microM), frequency, and severity of malformations and in decreased growth parameters. Protein and DNA contents of embryo and visceral yolk sac (VYS), likewise decreased significantly as lindane concentrations increased. Lindane exposures greater than 100 microM produced abnormal axial rotation, pooled blood on lateral cephalic surfaces, cephalic edema, and decreased VYS vasculature. Histologic sections showed a variety of abnormalities, including distended anterior cardinal veins, thinning of the neuroepithelium in forebrain and hindbrain regions, and abnormal branchial arch development. CYS and GSH levels in the VYS were not significantly affected by 100 microM lindane exposure during a 5-h incubation period on GD 10 and GD 11. In contrast, CYS and GSH levels in lindane-exposed embryos remained unchanged while control levels continued to increase with gestational age. At 5 h, treated embryos showed a significant depletion of CYS (GD 10, 22%; GD 11, 35%) and GSH (GD 10, 41%; GD 11, 24%) relative to controls. Selective lindane-induced depletion of embryonic GSH suggests involvement of the glutathione redox cycle in lindane embryotoxicity.
McNutt
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Department of Environmental and Industrial Health, University of Michigan, Ann Arbor 48109-2029.
Harris
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D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D015017:Yolk Sac / Q000187:drug effects / Q000378:metabolism*
D011506:Proteins; D013723:Teratogens; D001556:Hexachlorocyclohexane; D004247:DNA; D005978:Glutathione; D003545:Cysteine