- Full (HTML) - Full (PDF) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Pauliina Paakki,¹ Helene Stockmann,² Marjatta Kantola,³ Peruka Wagner,⁴ Urs Lauper,⁴ Renate Huch,⁴ Eivor Elovaara,² Pertti Kirkinen,⁵ and Markku Pasanen^1,6

¹Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland; ²Finnish Institute of Occupational Health, Helsinki, Finland; ³Department of Chemistry, University of Kuopio, Kuopio, Finland; ⁴Department of Obstetrics, University of Zürich, Zürich, Switzerland; ⁵Department of Gynecology and Obstetrics, University of Kuopio, Kuopio, Finland; ⁶National Agency for Medicines, Helsinki, Finland

Abstract

We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP) -mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD) , 7-ethoxycoumarin O-deethylase (ECOD) , pyrene 1-hydroxylase (P1OH) , and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II) , UDP-glucuronosyltransferase (UGT) , and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects ; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p < 0.001) , but not between ECOD and aromatase or P1OH and EROD activities ; we also found significant correlations between blood cotinine and UGT activities (p < 0.01) . In contrast, in controls (mothers who did not abuse drugs but did smoke cigarettes) , the P1OH activity correlated with ECOD, EROD (p < 0.001) , and testosterone hydroxylase (p < 0.001) activities. Our results (wider variation in ECOD activity among tissue from drug-abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes ; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy. Key words: barbiturates, benzodiazepines, cocaine, cytochrome P450, drug metabolism, gestation, methadone, opiates, pregnancy, smoking, steroids. Environ Health Perspect 108:141-145 (2000) . [Online 7 January 2000]

http://ehpnet1.niehs.nih.gov/docs/2000/108p141-145paakki/ abstract.html

Address correspondence to M. Pasanen, Department of Pharmacology and Toxicology, University of Oulu, PL 5000, 90401 Oulu, Finland. Telephone: 358-8-5375253. Fax: 358-8-5375247. E-mail: markku.pasanen@oulu.fi

The expert technical assistance of R. Heikkinen is gratefully acknowledged. This work was supported by The Academy of Finland grants No. 34555, 29456, European Commission, Biomed 2 Program project contracts (EUROCYP) and BMH4-97-2621.

Received 4 May 1999 ; accepted 26 August 1999.