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Sources and Impacts of Emerging Contaminants Nancy Denslow, Ph.D. Center for Environmental and Human Toxicology, UF Relationship between ECs and EDCs Emerging contaminants may have different modes of action Some may target the endocrine system It is important to determine not only the presence of the contaminants – but also that they cause biological effects in aquatic species It is important to determine whether the contaminants target growth, reproduction and susceptibility to disease Biomarkers Irreversible 50 n it o a l u p Po ue ol ec ul ar 100 Ti ss M Percent Measured Effect Reversible 0 nM uM mM Concentration of Toxicant Systems Toxicology Toxicant Phenotypic Anchoring Omics Databases Profiling Transcriptomics Proteomics Metabolomics Histopathology Reproduction Growth Survival Behavior changes Absorption, distribution Metabolism, excretion Toxicology Database Computational Analysis Systems Toxicology Effect of EDCs on Reproductive Endpoints with High Ecological Value EDC Genetics Food Egg number Energy Level Population Age Field study X Location of sites z no diff in behavior z aggressive behavior z feminized behavior Arrows point direction relative to sewage treatment facility 13 3 11 12 7 Analysis by microarray Fish ± Æ organ Æ total RNA Æ cDNA Æ array treatment Control 20 ng/L E2 100 ng/L E2 Liver Field Sites Gene expression profiles P<0.01 Gonad Gonad Biological Processes up-regulated site #12 vs site #11 1 2 3 4 5 6 7 8 9 10 11 12 Ras protein signal transduction female meiosis I acetylcholine receptor signaling activation of JNKK activity cholesterol absorption lipid digestion intestinal absorption sensory perception of taste cell communication male meiosis signal transduction activation of MAPKK activity 13 14 15 16 17 18 19 20 21 22 23 24 mitotic spindle checkpoint regulation of protein kinase activ regulation of transferase activity glutathione biosynthesis/metabol phototransduction, visible light I-kappaB kinase/NF-kappaB casc detection of visible light negative regulation of protein kin negative regulation of transferase protein kinase cascade neural crest cell migr/develop/diff aromatic amino acid family metab Gonad Biological Processes down-regulated site #12 vs site #11 1 2 3 4 5 6 7 10 11 13 17 18 innate immune response response to stress cellular physiological process complement activation, alternative iron ion homeostasis transition metal ion homeostasis cation homeostasis pre-replicative complex formation UDP-galactose transport embryonic genitalia morphogenes regulation of transcription complement activation 19 21 22 23 26 27 28 39 45 57 69 70 nucleotide-excision repair female meiosis chrom segregation reg. insulin receptor signaling regulation of cellular metabolism immune response response to wounding cell proliferation endoderm formation embryonic development regulation of cell growth nitric oxide metabolism genitalia development Conclusions Exposure of FHM for 48 hr to effluent is sufficient to get gene expression changes Changes in profiles suggest that fish could be adversely affected. A more thorough investigation of site #12 should be enacted to determine risk to aquatic organisms