Induction of CYP1A by carbofuran in primary culture of fish hepatocytes.
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.
Ghosh
M C
MC
Department of Animal Physiology, Bose Institute, Calcutta, India.
Ghosh
R
R
Ray
A K
AK
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002235:Carbofuran / Q000494:pharmacology*; D002397:Catfishes; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004790:Enzyme Induction; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D019324:beta-Naphthoflavone / Q000494:pharmacology
D001571:Benzoflavones; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D003513:Cycloheximide; D019363:Cytochrome P-450 CYP1A1; D002235:Carbofuran