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Induction of CYP1A by carbofuran in primary culture of fish hepatocytes

✍ Scribed by Manik C. Ghosh; Rama Ghosh; Arun K. Ray

Publisher: John Wiley and Sons
Year: 2000
Tongue: English
Weight: 137 KB
Volume: 14
Category: Article
ISSN: 1095-6670
DOI: 10.1002/(sici)1099-0461(2000)14:4<204::aid-jbt4>3.0.co;2-8

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✦ Synopsis

Carbofuran is a nematicide used in agricultural fields throughout the world. Indiscriminate use of this pesticide poses severe detrimental effects on our ecosystem. We have shown that it induces the CYP1A (cytochrome P4501A) monooxygenase enzyme system in cultured hepatocytes from Indian catfish, Heteropneustes fossilis (Bloch). We have quantified this induction by measuring the activity of the enzyme 7-ethoxyresorufin-O-deethylase (EROD), synthesized from CYP1A1 gene. The induction followed a dose-dependent relationship with carbofuran. The dose-dependent curve of EROD using carbofuran was very much similar with beta-napthoflavone, which is a known inducer of CYP1A1. Coexposure of these compounds to the culture media showed a synergistic effect on the enzyme activity. A blocker of aromatic hydrocarbon receptor, alpha-napthoflavone, blocked carbofuran-induced EROD activity in a dose-dependent manner. All these findings suggest that metabolism of carbofuran might be mediated by the CYP1A monooxygenase system through binding of the aromatic hydrocarbon receptor. We have also studied the superinduction phenomenon, which is a typical characteristic of the CYP1A gene in our system.

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