Xenobiotic and steroid-metabolizing monooxygenases catalysed by cytochrome P450 and glutathione S-transferase conjugations in the human placenta and their relationships to maternal cigarette smoking.
Placentae from both smoking and non-smoking mothers were studied with respect to P450-dependent xenobiotic and steroid-metabolizing reactions, GSHt activity with different substrates and umbilical blood cotinine levels. Catalytic activities were determined in both freshly prepared homogenate subfractions and subfractions prepared after freezing the tissue sample. The results showed three correlation clusters: (i) AHH and ECDE (P less than 0.001), (ii) ECDE and ERDE (P less than 0.05), and (iii) Arom and CSCC reactions correlated with each other both in the mitochondria and microsomes. Among xenobiotic and steroid metabolizing activities, only CSCC and AHH showed a significant negative correlation. Our results agree with the earlier studies (Gottlieb and Manchester, 1986) reporting that xenobiotic metabolising MO and GSHt reactions did not show any statistically significant correlations, reflecting the fact that maternal cigarette smoking does not affect GSHt activities. However, in placentae from smoking mothers a statistically significant (P less than 0.01) positive correlation between GSHt and Arom activity was found. No plausible biological explanation is available for this finding. Among xenobiotic-metabolizing activities only ERDE correlated with plasma cotinine levels, suggesting that it is most closely related to the extent of maternal cigarette smoking. The present findings also suggest that cigarette smoke induced ERDE activity is a distinct one compared with the other xenobiotic-metabolizing P450s. Negative correlations between xenobiotic-metabolizing MO activities and CSCC lend some support to an earlier suggestion (Juchau et al, 1972) that cigarette smoking affects endogenous steroid-metabolizing CSCC reaction catalyzed by P450. Whether this finding is a true biological phenomenon and what is the mechanism behind it remain to be elucidated.
Pasanen
M
M
University of Oulu, Department of Pharmacology and Toxicology, Finland.
Pelkonen
O
O
D003367:Cotinine / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000032:analysis; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects*; D013256:Steroids / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*
D013256:Steroids; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D003367:Cotinine