DEVELOPMENTAL REGULATION OF THE 3-METHYLCHOLANTHRENE-INDUCIBLE AND DIOXIN-INDUCIBLE CYP1A5 GENE IN CHICK-EMBRYO LIVER IN-VIVO

The cDNA sequences for two dioxin-inducible cytochrome P450s in chicke n, CYP1A4 and CYP1A5, have recently been reported which correspond to two dioxin-inducible forms of P450 previously designated as TCDDAHH an d TCDDAA, respectively. The developmental expression of CYP1A4-associa ted aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) activity and i ts association with expression of the Ah receptor had previously been characterized in chick embryo liver. The purpose of this study was to examine the developmental regulation of the second dioxin-inducible P4 50 gene, CYP1A5, in chick embryo liver. A partial gene sequence for CY P1A5 indicated that the intron/exon organization of this gene was iden tical to that of the CYP1A1 and CYP1A2 mammalian genes and was present in a single copy in the genome. CYP1A5 mRNA was expressed basally in chick embryo liver and was highly inducible by the Ah receptor ligands , 3-methylcholanthrene, beta-naphthoflavone, and 3,4,3',4'-tetrachloro biphenyl (TCB), but not by the phenobarbital analog, glutethimide. CYP 1A5 mRNA levels were increased 40- to 50-fold within 5 h after a singl e TCB treatment, corresponding to a 30- to 40-fold increase in the tra nscription rate of the CYP1A5 gene at this time point. In contrast to a previous report that CYP1A5 mRNA expression was inducible by estradi ol, we observed no effects of estradiol or dexamethasone on CYP1A5 mRN A expression, either alone or in combination with TCB. Basal and TCB-i nducible CYP1A5 mRNA expression was maximal in liver at 8 days of deve lopment and remained high throughout the remainder of embryonic develo pment. Thus, CYP1A5 appears to be regulated in a very similar manner t o CYP1A4 in chick embryo liver. (C) 1998 Academic Press.