Aromatase activity modulation by lindane and bisphenol-A in human placental JEG-3 and transfected kidney E293 cells.
Aromatase is the cytochrome P-450 involved in converting androgens to estrogens. The cytochrome P-450 family plays a central role in the oxidative metabolism of compounds including environmental pollutants. Since lindane and bisphenol-A (BPA) are two well-characterized endocrine disruptors that have been detected in animals and humans, it was important to learn whether they could affect aromatase activity and consequently estrogen biosynthesis. The present study investigates the effects of BPA and lindane on cytotoxicity, aromatase activity and mRNA levels in human placental JEG-3 cells and transfected human embryonal kidney 293 cells. Both cell lines were exposed to increasing concentrations of lindane (25, 50 and 75 microM) and bisphenol-A (25, 50 and 100 microM) over different time periods (10 min-18 h). As a result, none of these concentrations showed cytotoxicity. After short pre-incubation times (10 min-6 h), aromatase activity was enhanced by both compounds. Longer time incubation (18 h), however, produced dose-related inhibition. Lindane and BPA had no significant effects on CYP19 mRNA levels. Therefore, lindane and BPA modulate aromatase activity suggesting an interaction with the cytochrome P-450 aromatase. This study highlights the endocrine-modulating properties of lindane and bisphenol-A.
Nativelle-Serpentini
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C
IBBA - Laboratoire de Biochimie et Biologie Moléculaire - EA 2608 - Université de Caen, Esplanade de la Paix - 14032, Caen cedex, France.
Richard
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Séralini
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GE
Sourdaine
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P
D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors; D001559:Benzhydryl Compounds; D002460:Cell Line; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007668:Kidney / Q000201:enzymology*; D010636:Phenols / Q000633:toxicity*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D000098826:Bisphenol A Compounds
D000395:Air Pollutants, Occupational; D001141:Aromatase; D047072:Aromatase Inhibitors; D001559:Benzhydryl Compounds; D018076:DNA, Complementary; D001556:Hexachlorocyclohexane; D007306:Insecticides; D010636:Phenols; D012313:RNA; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C006780:bisphenol A; D000098826:Bisphenol A Compounds