Induction of cytochrome P-450S by alpha-naphthoflavone in primary cultures of adult rat hepatocytes

Abstract

To study the induction of drug metabolism associated to cytochrome P-450 by alpha-naphthoflavone(ANF), we determined specific cytochrome P-450 dependent monooxygenase activities according to culture time and dose of ANF by using specific substrate to each cytochrome P-450, especially phenobarbital(PB)- and 3-methylcholanthrene(MC)-inducible type of P-450, and compared with activity of in two media. We found that the activity of cytochrome P-450 dependent drug metabolism was increased by the addition of ANF to culture medium. This induction of cytochrome P-450 was also idemtified by the quantitation of P-450 mRNA using typespecific oligonucleotide probe in hybridization. Also we detected the inhibition of TCDD-mediated P-450 induction by ANF(10 uM) to examine whether the induction of cytochrome P-450 by ANF occur through the cytosolic Ah receptor. In conclusion, it seems that the induction of cytochrome P-450 by ANF may be occur by the accumulation of mRNA through receptor-ligand level.