Xenobiotic oxidation during early pregnancy in man: peroxidase catalysed chemical oxidation in conceptual tissues.
1. A membrane-bound peroxidase activity was isolated and purified from pooled samples of human intrauterine tissue (embryo, placenta, amnion, chorion and uterine decidua) of 4-6 weeks of gestation. 2. The H2O2-dependent guaiacol oxidation catalysed by the purified peroxidase exhibited a specific activity of 10.82 +/- 1.81 mumol/min/mg protein. 3. The optimum conditions required for guaiacol oxidation catalysed by the peroxidase included 18 mM guaiacol, 400 microM H2O2, pH 9.0, and 2 micrograms/ml enzyme protein. The guaiacol oxidation was inhibited by KCN and NaN3 with IC50s of 17.6 and 22 microM, respectively. 4. Several other endogenous and exogenous chemicals also underwent H2O2-dependent oxidation catalysed by the purified peroxidase. These results suggest that peroxidase may be one of the major pathways of xenobiotic oxidation present in organogenesis-stage human conceptual tissues influencing the toxicity of chemicals to which the developing embryo is exposed.
Toxicology Program, College of Public Health, MDC, University of South Florida, Tampa 33612.
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P
Joseph
S N
SN
Srinivasan
A P
AP
Kulkarni
D000650:Amnion / Q000201:enzymology; D001386:Azides / Q000494:pharmacology; D002384:Catalysis; D002823:Chorion / Q000201:enzymology; D003656:Decidua / Q000201:enzymology; D004622:Embryo, Mammalian / Q000201:enzymology; D005260:Female; D006801:Humans; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy / Q000378:metabolism*; D019810:Sodium Azide; D015262:Xenobiotics / Q000378:metabolism*
D001386:Azides; D015262:Xenobiotics; D011189:Potassium Chloride; D019810:Sodium Azide; D010544:Peroxidases