Rainbow trout cytochrome P450s: purification, molecular aspects, metabolic activity, induction and role in environmental monitoring

Buhler, Donald R.; Wang-Buhler, Jun-Lan

doi:10.1016/s0742-8413(98)10033-6

Cited by 98 publications

(95 citation statements)

References 164 publications

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“…Best documented is the presence of CYP1A in the head kidney (e.g., Lorenzana et al, 1988;Pesonen et al, 1990), spleen (Taysse et al, 1998), or in distinct immune cell populations (Nakayama et al, 2008). Particularly the work in Buhler's group showed expression of a series of other CYP transcripts in the kidney of trout, mainly within the CYP1 and CYP3 families, both of which could be responsible for tissue differences in BaP metabolites (reviewed in Buhler and Wang-Buhler, 1998). Tissue-specific differences in BaP metabolites, in fact, were observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

et al. 2013

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Polycyclic aromatic hydrocarbons (PAHs) are immunotoxicants in fish. In mammals, phase I metabolites are believed to be critically involved in the immunotoxicity of PAHs. This mechanism has been suggested for fish as well. The present study investigates the capacity of immune organs (head kidney, spleen) of rainbow trout, Oncorhynchus mykiss, to metabolize the prototypic PAH, benzo [a]pyrene (BaP). To this end, we analyzed 1) the induction of enzymatic capacity measured as 7-ethoxyresorufin-O-deethylase (EROD) activity in immune organs compared with liver, 2) the organ profiles of BaP metabolites generated in vivo, and 3) rates of microsomal BaP metabolite production in vitro. All measurements were done for control fish and for fish treated with an intraperitoneal injection of 15 mg BaP/kg body weight. In exposed trout, the liver, head kidney, and spleen contained similar levels of BaP, whereas EROD induction differed significantly between the organs, with liver showing the highest induction factor (132.83), followed by head kidney (38.43) and spleen (1.43). Likewise, rates of microsomal metabolite formation experienced the highest induction in the liver of BaP-exposed trout, followed by the head kidney and spleen. Microsomes from control fish displayed tissue-specific differences in metabolite production. In contrast, in BaP-exposed trout, microsomes of all organs produced the potentially immunotoxic BaP-7,8-dihydrodiol as the main metabolite. The findings from this study show that PAHs, like BaP, are distributed into immune organs of fish and provide the first evidence that immune organs possess inducible PAH metabolism leading to in situ production of potentially immunotoxic PAH metabolites.

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Section: Discussionmentioning

confidence: 99%

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

et al. 2013

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“…In addition, CYP3A27 has also been shown to catalyze N-demethylation of benzphetamine in rainbow trout (Miranda et al, 1989). Buhler & Wang-Buhler (1998) suggested that fish CYP3A27 and the mammalian CYP3A4 (the major CYP isoform studied in drug metabolism) are very similar in structure and catalytic function. Our findings on the constitutive CYP isoforms emphasize the role of the olfactory system, not only for normal development and behavior, but also its relevance from an environmental toxicology perspective.…”

Section: Discussionmentioning

confidence: 99%

“…In trout liver, the CYP1A1 isoform predominates (Cao et al, 2000). CYP1A1 mRNA is also constitutively expressed in Atlantic salmon and is inducible on exposure to polycyclic aromatic hydrocarbons (Buhler and Wang-Buhler, 1998;Rees and Li, 2004) . Although we could not discriminate between the two isoforms in the present study, it is reasonable to assume CYP1A1 mRNA was detected in our assays due to the predominant presence of this isoform in the closely related rainbow trout.…”

Section: Discussionmentioning

confidence: 99%

“…In fish, biotransformation enzymes are mostly distributed in the liver, although extra-hepatic sites also include the gut, the kidneys, the gills and the olfactory system (Stegeman, 1989;Smolowitz et al, 1992;Monod et al, 1994;Buhler & Wang-Buhler, 1998). The gills and the olfactory tissues, in particular, constitute direct target sites for waterborne pollutants given their intimate contact with the external environment (Klaprat et al, 1992;Wood, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Phase I biotransformation enzymes in coho salmon (Oncorhynchus kisutch)

Matsuo

Gallagher

Trute

et al. 2008

Comparative Biochemistry and Physiology Part C: Toxicology &

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Wild stocks of Pacific salmon in the Northwestern United States have declined in recent years, and the major factors contributing to these losses include water pollution and loss of habitat. In salmon, sublethal chemical exposures may impact critical behaviors (such as homing, feeding, predatoravoidance) that are important for species survival. Therefore, understanding the potential for these species to biotransform organic compounds within sensitive target tissues such as liver, gills and olfactory region can help estimate or predict their susceptibility to pollutants. In this study, we used real-time quantitative polymerase chain reaction (Q-PCR), Western blotting, and catalytic assays to characterize the expression of Phase I biotransformation enzymes in coho salmon (Oncorhynchus kisutch), a sensitive species in the Pacific Northwest. Gene expression analysis using Q-PCR assays developed for coho genes revealed the presence of the predominant cytochrome P450 mRNAs (CYP1A, CYP2K1, CYP2M1, CYP3A27) in the olfactory rosettes and provided quantitative mRNA expression levels in coho liver and gills. Q-PCR analysis revealed relatively high expression of the major CYP isoforms in the liver and olfactory rosettes, which was generally confirmed by Western blotting. Extrahepatic CYP expression was generally higher in the olfactory rosettes as compared to the gills. Catalytic studies demonstrated functional CYP1A-dependent ethoxyresorufin-Odeethylase, CYP2-dependent pentoxyresorufin-O-dealkylase, CYP2K1-dependent testosterone 16β-hydroxylase, and CYP3A27-dependent testosterone 6β-hydroxylase activities in liver, but not at detectable levels in gills. In contrast, flavin-containing monooxygenase (FMO)-dependent thiourea S-oxidase activity was readily observed in the gills and was substantially higher than that observed in liver. Collectively, the results of this study suggest that the olfactory rosettes are important sites of extrahepatic biotransformation in coho salmon, and that tissue specific-differences in Phase I metabolism may lead to contrasting tissue-specific biotransformation capabilities in coho salmon.

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“…CYP1A and CYP3A have been shown to metabolize endogenous steroids and detoxify drugs and environmental chemicals. [77][78][79][80][81][82][83] The liver is the main site for steroid metabolism, although some activity can also be found in other tissues. 84) Many studies have shown that compounds that affect the synthesis or metabolism of steroids are responsible for changes in circulating steroid levels.…”

Section: Endocrine-disrupting Effectsmentioning

confidence: 99%

Applications of genomic technologies to the study of organochlorine pesticide-induced reproductive toxicity in fish

García-Reyero

Denslow

2006

J. Pestic. Sci.

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Rainbow trout cytochrome P450s: purification, molecular aspects, metabolic activity, induction and role in environmental monitoring

Cited by 98 publications

References 164 publications

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

Characterization of Phase I biotransformation enzymes in coho salmon (Oncorhynchus kisutch)

Applications of genomic technologies to the study of organochlorine pesticide-induced reproductive toxicity in fish

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