How do biomarkers dance? Specific moves of defense and damage biomarkers for biological interpretation of dose-response model trends.

Abstract

Omics and multi-omics studies are currently increasingly used in ecotoxicology to highlight the induction of known or new biomarkers when an organism is exposed to one (or more) contaminant(s). Although it is virtually impossible to identify all biomarkers from all possible organisms, biomarkers can be grouped into two categories, defense or damage biomarkers and they have a limited number of response trends. Our working hypothesis is that defense and damage biomarkers show different dose-response patterns. A meta-analysis of 156 articles and 2,595 observations of dose-response curves of well-known defense and damage biomarkers was carried out in order to characterize the response trends of these biological parameters in a large panel of living organisms (18 phyla) exposed to a wide variety of inorganic or organic contaminants. Defense biomarkers describe biphasic responses (bell-shaped and U-shaped) to a greater extent than damage biomarkers. In contrast, damage biomarkers varied mainly monotonically (decreasing or increasing). Neither the nature of the contaminant nor the type of organisms, whatever the kingdom (Plantae, Animalia, Chromista or Bacteria), influence these specific responses. This result suggests that cellular defense and damage mechanisms are not specific to stressors and are conserved throughout life. The meta-analysis results confirm the usefulness of trend analysis in dose-response models as a biological interpretation of biomarkers in large dataset and their application in determining the concentration ranges inducing defense responses (CRIDeR) and the concentration ranges inducing damage responses (CRIDaR) regardless of the contaminant tested or the organism studied. HighlightsO_LIWe interpreted 2,595 biomarker dose-response curves generated by chemical exposure. C_LIO_LIDefense biomarkers mainly describe biphasic (bell- or U-shaped) trends. C_LIO_LIDamage biomarkers mainly describe monotonic (decreasing or increasing) trends. C_LIO_LICellular defense and damage responses appear to have been conserved during evolution. C_LIO_LIResponse trend analysis is a promising tool for environmental risk assessment. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/551999v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@14b19c4org.highwire.dtl.DTLVardef@188ae31org.highwire.dtl.DTLVardef@643ed6org.highwire.dtl.DTLVardef@15953cd_HPS_FORMAT_FIGEXP M_FIG C_FIG