Developmental regulation of the 3-methylcholanthrene- and dioxin-inducible CYP1A5 gene in chick embryo liver in vivo.
The cDNA sequences for two dioxin-inducible cytochrome P450s in chicken, CYP1A4 and CYP1A5, have recently been reported which correspond to two dioxin-inducible forms of P450 previously designated as TCDDAHH and TCDDAA, respectively. The developmental expression of CYP1A4-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 for CYP1A5 indicated that the intron/exon organization of this gene was identical 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'-tetrachlorobiphenyl (TCB), but not by the phenobarbital analog, glutethimide. CYP1A5 mRNA 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 the CYP1A5 gene at this time point. In contrast to a previous report that CYP1A5 mRNA expression was inducible by estradiol, we observed no effects of estradiol or dexamethasone on CYP1A5 mRNA expression, either alone or in combination with TCB. Basal and TCB-inducible CYP1A5 mRNA expression was maximal in liver at 8 days of development and remained high throughout the remainder of embryonic development. Thus, CYP1A5 appears to be regulated in a very similar manner to CYP1A4 in chick embryo liver.
Bentivegna
C S
CS
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, 03755-3835, USA.
Ihnat
M A
MA
Baptiste
N S
NS
Hamilton
J W
JW
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D008748:Methylcholanthrene / Q000633:toxicity*; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D012689:Sequence Homology, Nucleic Acid; D015262:Xenobiotics / Q000633:toxicity*
D018076:DNA, Complementary; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D015262:Xenobiotics; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C108015:cytochrome P-450 CYP1A5