Transcriptome responses to carbon tetrachloride and pyrene in the kidney and liver of juvenile rainbow trout ( Oncorhynchus mykiss)

Abstract

We report the effects of the hepatotoxic compound carbon tetrachloride (CCl 4) and pyrene, a model polycyclic aromatic hydrocarbon, on the transcriptomes of juvenile rainbow trout kidneys and livers. Fish were exposed to sublethal doses for 4 days and expression of 1273 genes was measured using a cDNA microarray. Efforts were focused on differentiating between unspecific responses and those that can be regarded as molecular signatures of CCl 4 and pyrene toxicities. Expression profiles were analyzed in terms of Gene Ontology categories. Universal reactions to chemical toxicity were observed in metallothionein, HSP90 and mitochondrial proteins of oxidative phosphorylation, which were induced in both tissues. Several genes showed similar responses to both compounds in either kidney or liver; most of the effects are implicated in hematopoiesis and immune response. Stimulation of mitochondrial and heat shock proteins was greater in the liver than in the kidney, whereas genes involved in transcription, humoral immune response and apoptosis were suppressed. Pyrene and CCl 4 caused opposite effects on expression of several genes, including HSP-27, macrophage receptor Marco, metalloproteinases (MMP9 and MMP13), and delta-6 fatty acid desaturase. Pyrene affected mainly genes implicated in the maintenance of the genetic apparatus, immune response, glycolysis, and iron homeostasis. CCl 4 affected the structural proteins and genes involved in cellular stress, protein folding, and steroid metabolism. Overall, pyrene suppressed a range of protective or acclimative reactions, many of which were stimulated with CCl 4. Additionally, gene profiling analyses indicated adaptive and potentially maladaptive reactions to toxicity. For instance, stimulation of mitochondrial proteins coincided with suppression of catalase, whereas CCl 4 down-regulated fatty acid metabolism and peroxisomal proteins. A number of candidate biomarkers for ecotoxicological risk assessment were identified as our understanding of mechanisms of pyrene and CCl 4 toxicities in rainbow trout increased.