title: Effects of reactive oxygen metabolites on erythropoietin production in renal carcinoma cells.
abstract: The present studies were undertaken to determine the effects of reactive oxygen metabolites on erythropoietin (Ep) biosynthesis in Ep-producing renal carcinoma (RC) cells using a sensitive radioimmunoassay for Ep. Xanthine (10-5M) and increasing concentrations of xanthine oxidase (8 x 10(-7) to 5 x 10(-4) units/ml) produced a significant dose-related increase in Ep production at a concentration of greater than or equal to 4 x 10(-6) units/ml, whereas xanthine alone had no effect. Catalase, a scavenger of hydrogen peroxide (H2O2), in concentrations of 50 to 500 micrograms/ml produced a significant inhibition of the increase in Ep production induced by xanthine-xanthine oxidase; while no effect was seen on basal levels of Ep production and the growth of RC cells. Glucose oxidase (greater than or equal to 0.032 mU/ml), a direct H2O2 generator, and exogenous H2O2 (greater than or equal to 4 x 10(-6)M) added to the incubation mixture, caused a significant enhancement of Ep production in a dose-dependent manner. Xanthine-xanthine oxidase, glucose oxidase, and H2O2 in the above concentrations did not produce significant cytotoxicity (51Cr release or trypan blue dye exclusion). The present data suggests that H2O2, a reactive oxygen metabolite may play a significant role in Ep production.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: J
authors.initials: J
authors.lastname: Brookins
authors.forename: B S
authors.initials: BS
authors.lastname: Beckman
authors.forename: J W
authors.initials: JW
authors.lastname: Fisher
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D004921:Erythropoietin / Q000096:biosynthesis*; D005949:Glucose Oxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010100:Oxygen / Q000378:metabolism*; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
chemical_list: D014970:Xanthines; D004921:Erythropoietin; D019820:Xanthine; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D002374:Catalase; D014969:Xanthine Oxidase; D010100:Oxygen