Effect of acute lead treatment on coproporphyrinogen oxidase activity in HepG2 cells.
Acute toxic effects of lead were evaluated on porphyrin synthesis and coproporphyrinogen oxidase (CO) activity in an in vitro model, using HepG2 cells, a hepatoma cell line of human origin. Lead concentrations for exposure treatments were 0.5, 1.0, 2.5, 5.0 microM. No significant changes were found in treated cells with respect to uroporphyrin cellular or media concentrations. Cellular protoporphyrin increased in dose response shape, but no changes in extracellular content were found. Extracellular coproporphyrin concentration increased in a dose response manner without changes in cellular content. The CO activity was depressed in dose response shape, reaching 62% of control activity at 5.0 microM of lead treatment. The CO activity in Pb-treated cells was recovered after dithiothreitol (DTT) treatment, suggesting that sulphydryl groups play an essential role in the enzyme activity. The dose-response increase of coproporphyrin secretion accompanied by the depression of CO activity supports the suggestion that lead causes CO inhibition, as observed in this cellular model.
Hernández
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Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, México DF, Mexico.
Gutiérrez-Ruiz
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MC
Garciá Vargas
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D006528:Carcinoma, Hepatocellular; D002851:Chromatography, High Pressure Liquid; D003304:Coproporphyrinogen Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007854:Lead / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity*; D011524:Protoporphyrins / Q000032:analysis / Q000096:biosynthesis; D013050:Spectrometry, Fluorescence; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D009942:Organometallic Compounds; D011524:Protoporphyrins; D013439:Sulfhydryl Reagents; D007854:Lead; D003304:Coproporphyrinogen Oxidase; C008261:lead acetate; D004229:Dithiothreitol