Epoxide hydrolase and aryl hydrocarbon hydroxylase in human fetal tissues: activities in nuclear and microsomal fractions and in isolated hepatocytes.
Epoxide formation from drugs, chemicals, food additives and environmental pollutants is catalyzed by cytochrome P-450 dependent monooxygenase(s). Epoxides are converted to glycols or dihydrodiols by epoxide hydrolase (EH). These enzymes are known to be present in the microsomes of different mammalian tissues and in the hepatic nuclei from rats and humans. The balance between the epoxide forming (AHH) and metabolizing (EH) enzyme activities may provide information about the "epoxide exposure" of a tissue. We thus investigated AHH and EH in the nuclear and microsomal fractions from six livers, four kidneys, four lungs, and two adrenals from human fetuses (gestational age between 15 and 24 weeks). Tissues were obtained at legal abortion for sociomedical reasons. AHH activity was measured according to van Cantfort et al (Biochem Biophys Res Commun 79: 505, 1977) using beno (a)pyrene as substrate. EH was measured as described by Jerina et al (Mol Pharmacol 13:342, 1977) using both styrene oxide (SO) and benzo(a)pyrene-4,5-oxide (BPO) as substrate. The nuclear fraction was isolated by a multistep procedure including centrifugation in high density sucrose ( Pacifici et al, unpublished). The hepatic AHH activity (pmole/min/mg; mean +/- SEM) was 11.5 +/- 2.2 in the nuclear fraction and 34.7 +/- 1.7 in the microsomes. In adrenals it was 6.0 (nuclei) and 4.4 (microsomes). The nuclear fraction from kidneys and lungs did not catalyze this reaction at a measurable rate, whereas microsomal AHH activity was 1.3 +/- 0.3 and 5.3 +/- 1.1, respectively, in these tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
D000311:Adrenal Glands; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D046508:Culture Techniques; D004851:Epoxide Hydrolases / Q000378:metabolism*; D005333:Fetus; D006801:Humans; D007668:Kidney; D008099:Liver; D008168:Lung; D008861:Microsomes / Q000201:enzymology; D013347:Subcellular Fractions / Q000201:enzymology
D001189:Aryl Hydrocarbon Hydroxylases; D004851:Epoxide Hydrolases