title: Effects of salinity acclimation on the pesticide-metabolizing enzyme flavin-containing monooxygenase (FMO) in rainbow trout (Oncorhynchus mykiss).
abstract: Thioether-containing pesticides are more toxic in certain anadromous and catadromous fish species that have undergone acclimation to hypersaline environments. Enhanced toxicity has been shown to be mediated through the bioactivation of these xenobiotics by one or more flavin-containing monooxygenases (FMOs), which are induced by hyperosmotic conditions. To better understand the number of FMO genes that may be regulated by hyperosmotic conditions, rainbow trout (Oncorhynchus mykiss) were maintained and acclimated to freshwater (<0.5 g/L salinity) and to 18 g/L salinity. The expression of 3 different FMO transcripts (A, B and C) and associated enzymatic activities methyl p-tolyl sulfoxidation (MTSO) and benzydamine N-oxigenation (BZNO) were measured in four tissues. In freshwater-acclimated organisms FMO catalytic activities were as follows: liver>kidney>gills=olfactory tissues; in hypersaline-acclimated animals activities were higher in liver>gills>olfactory tissues>kidney. Acclimation to 18 g/L caused a significant induction in the stereoselective formation of R-MTSO in gill. In olfactory tissues, stereoselective (100%) formation of S-MTSO was observed and was unaltered by acclimation to hypersaline water. When specific transcripts were evaluated, salinity-acclimation increased FMO A in liver (up to 2-fold) and kidney (up to 3-fold) but not in olfactory tissues and gills. FMO B mRNA was significantly down-regulated in all tissues, and FMO C was unchanged by hypersaline acclimation. FMO B and C failed to correlate with any FMO catalytic activity, but FMO A mRNA expression linearly correlated to both FMO catalytic activities (MTSO and BZNO) in liver (r(2)=0.92 and r(2)=0.88) and kidney microsomes (r(2)=0.93 and r(2)=90). FMO A only correlated with MTSO activity in gills (r(2)=0.93). These results indicate unique tissue specific expression of FMO genes in salmonids and are consistent with salinity-mediated enhancement of thioether-containing pesticide bioactivation by FMO which may occur in liver or kidney after salinity acclimation.
authors.affiliation: Department of Environmental Sciences, University of California, Riverside, 92521, USA. lavado.ramon@ucr.edu
authors.forename: Ramon
authors.initials: R
authors.lastname: Lavado
authors.forename: Rosaura
authors.initials: R
authors.lastname: Aparicio-Fabre
authors.forename: Daniel
authors.initials: D
authors.lastname: Schlenk
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D001591:Benzydamine / Q000378:metabolism; D055162:Biocatalysis / Q000187:drug effects; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005880:Gills / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D009830:Olfactory Bulb / Q000201:enzymology / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D010575:Pesticides / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012451:Safrole / Q000031:analogs & derivatives / Q000378:metabolism; D054712:Salinity; D017386:Sequence Homology, Amino Acid; D012965:Sodium Chloride / Q000494:pharmacology; D013379:Substrate Specificity; D013440:Sulfides / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D007527:Isoenzymes; D010575:Pesticides; D013440:Sulfides; C544071:methyl 4-tolylsulfide; D012965:Sodium Chloride; D001591:Benzydamine; D010088:Oxidoreductases; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D012451:Safrole; C005746:sulfoxide