Aryl hydrocarbon hydroxylase activity in the first-trimester human placenta: induction by carcinogens and chemoprotectors.
The activity of aryl hydrocarbon hydroxylase (AHH) was measured in the placenta using radioenzymatic techniques and benzo(a)pyrene (BP) as substrate. The optimal assay conditions were defined, including cofactor dependence. The Km of BP to the enzyme was 2 microM and Vmax 0.02 nmol/min. When compared to the AHH activity at term (0.35 +/- 0.03; mean +/- SEM), 1st-trimester activity was significantly lower (0.18 +/- 0.05; p less than 0.05). However, in the rat liver the enzyme activity was even higher than that found at term. In order to determine whether the 1st-trimester placental AHH activity is sensitive to environmental exposures, explants were incubated with two classes of xenobiotics: carcinogens and chemoprotectors. The carcinogen BP at 50 microM caused a significant (2.7-fold; p less than 0.05) increase in the enzyme activity after an incubation period of 6 h. After an incubation period of 24 h, however, no effect was noted. In contrast, 50 microM 20-methylcholanthrene had no effect. The effect of chemoprotectors was also examined: at 25 microM, coumarin, 2-(3)-tert-butyl-4-hydroxy-anisole, and 1-phenylazo-2-naphthol significantly increased 1.7, 1.7-, and 1.8-fold, respectively, the enzyme activity after an incubation period of 24 h (p less than 0.05). In conclusion, AHH in the 1st-trimester placenta is sensitive to environmental exposures and is induced in vitro by both carcinogen and chemoprotectors.
Barnea
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Fetoplacental Endocrine Unit, Rappaport Institute, Technion, Haifa, Israel.
Avigdor
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D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000502:physiology*; D002274:Carcinogens, Environmental / Q000378:metabolism*; D004796:Clinical Enzyme Tests; D005260:Female; D006801:Humans; D008297:Male; D010920:Placenta / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D015262:Xenobiotics / Q000378:metabolism*
D002274:Carcinogens, Environmental; D015262:Xenobiotics; D001189:Aryl Hydrocarbon Hydroxylases