New cytochrome P450 1B1, 1C2 and 1D1 genes in the killifish Fundulus heteroclitus: Basal expression and response of five killifish CYP1s to the AHR agonist PCB126

• Published in: Aquatic toxicology Vol. 93; no. 4; pp. 234 - 243
• Main Authors: Zanette, Juliano, Jenny, Matthew J., Goldstone, Jared V., Woodin, Bruce R., Watka, Lauren A., Bainy, Afonso C.D., Stegeman, John J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 26-07-2009; Elsevier
• Subjects: Agnatha. Pisces; AHR agonist; Amino Acid Sequence; Animal, plant and microbial ecology; Animals; Applied ecology; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Biological and medical sciences; Brackish; Cloning, Molecular; CYP1; Cytochrome P-450 CYP1B1; Cytochrome P-450 Enzyme System - classification; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Ecotoxicology, biological effects of pollution; Fish; Fundamental and applied biological sciences. Psychology; Fundulidae - genetics; Fundulus heteroclitus; Gene Expression - drug effects; General aspects; Molecular Sequence Data; P450; PCB; Pollution; Polychlorinated Biphenyls - pharmacology; Receptors, Aryl Hydrocarbon - agonists; Vertebrates: general zoology, morphology, phylogeny, systematics, cytogenetics, geographical distribution; Pollution; CYP1; Fish; AHR agonist; P450; PCB; Fundulus heteroclitus; Agonist; Ecotoxicology; Toxicity; Cytochrome P450; Biological marker; Polychlorobiphenyls; Freshwater environment; Aquatic environment; Vertebrata; Pisces
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2009.05.008

Knowledge of the complement of cytochrome P450 (CYP) genes is essential to understanding detoxification and bioactivation mechanisms for organic contaminants. We cloned three new
CYP1 genes,
CYP1B1,
CYP1C2 and
CYP1D1, from the killifish
Fundulus heteroclitus, an important model in environmental toxicology. Expression of the new
CYP1s along with previously known
CYP1A and
CYP1C1 was measured by qPCR in eight different organs. Organ distribution was similar for the two
CYP1Cs, but otherwise patterns and extent of expression differed among the genes. The AHR agonist 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) (31
pmol/g fish) induced expression of
CYP1A and
CYP1B1 in all organs examined, while
CYP1C1 was induced in all organs except testis. The largest changes in response to PCB126 were induction of
CYP1A in testis (∼700-fold) and induction of
CYP1C1 in liver (∼500-fold).
CYP1B1 in liver and gut,
CYP1A in brain and
CYP1C1 in gill also were induced strongly by PCB126 (>100-fold).
CYP1C1 expression levels were higher than
CYP1C2 in almost all tissues and
CYP1C2 was much less responsive to PCB126. In contrast to the other genes,
CYP1D1 was not induced by PCB126 in any of the organs. The organ-specific response of
CYP1s to PCB126 implies differential involvement in effects of halogenated aromatic hydrocarbons in different organs. The suite of inducible CYP1s could enhance the use of
F. heteroclitus in assessing aquatic contamination by AHR agonists. Determining basal and induced levels of protein and the substrate specificity for all five CYP1s will be necessary to better understand their roles in chemical effects and physiology.