Department of Environmental Sciences, University of California, Riverside, 92521, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2013 Jan;157(1):9-15. doi: 10.1016/j.cbpc.2012.08.004. Epub 2012 Sep 6.
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.
含硫醚的农药在某些洄游和溯河洄游鱼类中毒性更大,这些鱼类已经适应了高盐环境。研究表明,这些外源性物质的生物活化是通过一种或多种黄素单加氧酶(FMOs)介导的,而 FMOs 是由高渗条件诱导产生的。为了更好地了解可能受高渗条件调节的 FMO 基因数量,虹鳟(Oncorhynchus mykiss)被维持并适应于淡水(<0.5 g/L 盐度)和 18 g/L 盐度。在四个组织中测量了 3 种不同的 FMO 转录本(A、B 和 C)的表达和相关的酶活性甲基对甲苯亚砜(MTSO)和苯并达明 N-氧化(BZNO)。在适应淡水的生物体中,FMO 催化活性如下:肝>肾>鳃=嗅觉组织;在适应高渗的动物中,肝>鳃>嗅觉组织>肾的活性较高。适应 18 g/L 盐度会导致鳃中 R-MTSO 的立体选择性形成显著增加。在嗅觉组织中,观察到 S-MTSO 的立体选择性(100%)形成,并且适应高渗水不会改变。当评估特定的转录本时,盐度适应会增加肝(高达 2 倍)和肾(高达 3 倍)中的 FMO A,但不会增加嗅觉组织和鳃中的 FMO A。FMO B mRNA 在所有组织中均显著下调,而 FMO C 不受高渗适应的影响。FMO B 和 C 与任何 FMO 催化活性均无相关性,但 FMO A mRNA 表达与肝(r²=0.92 和 r²=0.88)和肾微粒体(r²=0.93 和 r²=90)中的两种 FMO 催化活性呈线性相关。FMO A 仅与鳃中的 MTSO 活性相关(r²=0.93)。这些结果表明鲑鱼科鱼类中存在独特的组织特异性 FMO 基因表达,并且与 FMO 介导的含硫醚农药生物活化增强一致,这种增强可能发生在盐度适应后的肝或肾中。