Developmental Regulation of the 3-Methylcholanthrene- and Dioxin-InducibleCYP1A5Gene in Chick Embryo Liverin Vivo

Abstract

The cDNA sequences for two dioxin-inducible cytochrome P450s in chicken,CYP1A4andCYP1A5,have recently been reported which correspond to two dioxin-inducible forms of P450 previously designated as TCDDAHHand TCDDAA, respectively. The developmental expression ofCYP1A4-associated aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) activity and its 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 P450 gene,CYP1A5,in chick embryo liver. A partial gene sequence forCYP1A5indicated that the intron/exon organization of this gene was identical to that of theCYP1A1andCYP1A2mammalian genes and was present in a single copy in the genome.CYP1A5mRNA was expressed basally in chick embryo liver and was highly inducible by the Ah receptor ligands, 3-methylcholanthrene, β-naphthoflavone, and 3,4,3′,4′-tetrachlorobiphenyl (TCB), but not by the phenobarbital analog, glutethimide.CYP1A5mRNA levels were increased 40- to 50-fold within 5 h after a single TCB treatment, corresponding to a 30- to 40-fold increase in the transcription rate of theCYP1A5gene at this time point. In contrast to a previous report thatCYP1A5mRNA expression was inducible by estradiol, we observed no effects of estradiol or dexamethasone onCYP1A5mRNA expression, either alone or in combination with TCB. Basal and TCB-inducibleCYP1A5mRNA expression was maximal in liver at 8 days of development and remained high throughout the remainder of embryonic development. Thus,CYP1A5appears to be regulated in a very similar manner toCYP1A4in chick embryo liver.