Time- and concentration-dependent metabolic and genomic responses to exposure to resin acids in brown trout (Salmo trutta m. lacustris).

The presence of metabolically conjugated resin acids (RAs) in the bile is considered to be a sensitive indicator for exposure of fish to pulp and paper industry effluents; however, to our knowledge, no comprehensive kinetic study of this response has been made. Juvenile brown trout (Salmo trutta m. lacustris) were exposed to a waterborne mixture of seven RAs (wood rosin) in time (0.1-192.0 h; average concentration, 8 microg/L) and dose (average concentrations, 0, 0.6, 4, 14, and 78 microg/L; 10 d) series, and total RAs were analyzed in bile. In time-dependent exposure, total RAs in bile increased up to 24 h. In concentration-dependent exposure, RAs increased along with the concentration of RAs in water, revealing a high-capacity biotransformation and elimination system in trout liver. In concentration-dependent exposures, the effects on the hepatic transcriptome was studied using a high-density cDNA microarray, and dose-dependent changes were found in a large number of genes. Resin acids interfered with iron metabolism, as evidenced by the decrease in transcripts for iron transporters and heme-containing proteins. Expression of genes encoding for enzymes degrading reactive oxygen species also decreased. Coordinated down-regulation of the protein biosynthesis machinery could result from inhibition of the energy metabolism. A number of changes in gene expression indicated recovery and remodeling of hepatic tissues. We conclude that analysis of total RAs in the bile provides a sensitive and quantitative tool for assessing the exposure of fish to waterborne RAs, whereas multiple gene expression analyses are able to elucidate simultaneous cellular functions for use as potential biomarkers of RAs.