Publication Date:
2022-05-25
Description:
Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 93 (2009): 234-243, doi:10.1016/j.aquatox.2009.05.008.
Description:
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.
Description:
This study was supported in part by NIH grants JJS (the Superfund Basic Research Program
5P42ES007381 and R01ES015912) and MJJ (K99ES017044-01).
Keywords:
P450
;
CYP1
;
Fundulus heteroclitus
;
Fish
;
PCB
;
AHR agonist
;
Pollution
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
Format:
application/pdf
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