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Addressing species diversity in biotransformation: variability in expressed transcripts of hepatic biotransformation enzymes among fishes
Fay, K., C. LaLone, D. Feifarek, J. Doering, J. Cavallin, Dan Villeneuve, S. Glaberman, AND G. Ankley. Addressing species diversity in biotransformation: variability in expressed transcripts of hepatic biotransformation enzymes among fishes. SETAC Europe, Rome, ITALY, May 13 - 17, 2018.
Adverse Outcome Pathways (AOPs) offer a mechanistic means to connect biological effects measured in vitro to outcomes relevant for chemical risk assessment. To employ AOPs for risk assessment, the chemical exposure at the target site must be known; however, an organism’s ability to biotransform xenobiotics is one of the greatest uncertainties in making a prediction of target site concentration. The present study characterizes the diversity of hepatic xenobiotic metabolizing enzymes among fishes. Data for this work was mined from available fish liver transcriptome data (PhyloFish database) and produced from liver tissue samples from 2 dozen divergent fish species, using a novel, full-transcript, isoform sequencing approach. This later approach eliminated the need for transcriptome reconstruction resulting in reference genomes of the highest precision, allowing for detection of enzyme isoform orthologs among the species. Species were selected for broad phylogenetic coverage, as well as economic, research, and conservation importance. Importantly, model test organisms used in toxicity testing were also included to evaluate how representative their biotransformational capacity may be for a broader range of species. The present work addresses AOPDD product needs regarding taxonomic applicability (Task 1.1C).
There is increasing evidence that diverse xenobiotic metabolizing enzymes exist among fishes, potentially resulting in different chemical sensitivities and accumulation, but this has never been systematically evaluated. One concern is that model test species such as rainbow trout, zebrafish and fathead minnows may not adequately represent the xenobiotic metabolizing capacity of other fish species. Our current study mined available fish liver transcriptome data and performed full-transcript, isoform sequencing on liver samples from two dozen phylogenetically diverse fish species. This novel RNAseq approach eliminated the need for transcriptome reconstruction resulting in reference genomes of the highest precision, allowing for detection of enzyme isoform orthologs among the species, as well as the nuclear receptors that control expression of the enzymes. Species were selected for broad phylogenetic coverage, as well as economic, research, and conservation importance, and included: sea lamprey (Petromyzon marinus), lake sturgeon (Acipenser fluvenscens), American eel (Anguilla rostrate), alligator gar (Atractosteus spatula), paddlefish (Polyodon spathula), rainbow trout (Oncorhynchus mykiss), rainbow smelt (Osmerus mordax), fathead minnow (Pimephales promelas), Antarctic icefish (Trematomus loennbergii), common carp (Cyprinus carpio), and channel catfish (Ictalurus punctatus). In addition to comparing information across fish species, the resolved isoforms were compared to human xenobiotic metabolizing enzymes. This comparison aids in evaluating the utility of human-based biotransformation tools such as ToxCast chemical screening assays or metabolism prediction software for potential relevance in fish.