Basal and 3,3',4,4',5-pentachlorobiphenyl-induced expression of cytochrome P450 1A, 1B and 1C genes in zebrafish

Jonsson, M.E., Orrego, R., Woodin, B.R., Goldstone, J.V., and Stegeman, J.J.
Toxicology and applied pharmacology   221(1): 29-41 (Journal)
Registered Authors
Goldstone, Jed, Stegeman, John J.
Cytochrome P4501 (CYP1); 3,32,4,42,5-Polychlorinated biphenyl (PCB126); Real-time PCR; Zebrafish
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Aryl Hydrocarbon Hydroxylases/genetics
  • Cloning, Molecular
  • Cytochrome P-450 CYP1A1/genetics
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 Enzyme System/genetics*
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Estrogen Antagonists/administration & dosage
  • Estrogen Antagonists/pharmacology
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Enzymologic/drug effects
  • Isoenzymes/genetics
  • Male
  • Molecular Sequence Data
  • Polychlorinated Biphenyls/administration & dosage
  • Polychlorinated Biphenyls/pharmacology*
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • beta-Naphthoflavone/pharmacology
17445853 Full text @ Tox. App. Pharmacol.
The cytochrome P4501C (CYP1C) gene subfamily was recently discovered in fish, and zebrafish (Danio rerio) CYP1C1 transcript has been cloned. Here we cloned the paralogous CYP1C2, showing that the amino acid sequence is 78% identical to CYP1C1, and examined gene structure and expression of CYP1A, CYP1B1, CYP1C1, and CYP1C2. Xenobiotic response elements were observed upstream of the coding regions in all four genes. Zebrafish adults and embryos were exposed (24 h) to 100 nM 3,3',4,4',5-polychlorinated biphenyl (PCB126) or 20 ppm acetone and subsequently held in clean water for 24 h (adults) or 48 h (embryos). All adult organs examined (eye, gill, heart, liver, kidney, brain, gut, and gonads) and embryos showed basal expression of the four genes. CYP1A was most strongly expressed in liver, whereas CYP1B1, CYP1C1, and CYP1C2 were most strongly expressed in heart and eye. CYP1B1 and the CYP1C genes showed an expression pattern similar to one another and to mammalian CYP1B1. In embryos CYP1C1 and CYP1C2 tended to have a higher basal expression than CYP1A and CYP1B1. PCB126 induced CYP1A in all organs, and CYP1B1 and CYP1C1 in all organs except gonads, or gonads and brain, respectively. CYP1C2 induction was significant only in the liver. However, in embryos all four genes were induced strongly by PCB126. The results are consistent with CYP1C1 and CYP1C2, as well as CYP1A and CYP1B1, being regulated by the aryl hydrocarbon receptor. While CYP1A may have a protective role against AHR agonists in liver and gut, CYP1B1, CYP1C1, and CYP1C2 may also play endogenous roles in eye and heart and possibly other organs, as well as during development.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes