title: Linkage of genomic biomarkers to whole organism end points in a Toxicity Identification Evaluation (TIE).
abstract: Aquatic organisms are exposed to many toxic chemicals and interpreting the cause and effect relationships between occurrence and impairment is difficult. Toxicity Identification Evaluation (TIE) provides a systematic approach for identifying responsible toxicants. TIE relies on relatively uninformative and potentially insensitive toxicological end points. Gene expression analysis may provide needed sensitivity and specificity aiding in the identification of primary toxicants. The current work aims to determine the added benefit of integrating gene expression end points into the TIE process. A cDNA library and a custom microarray were constructed for the marine amphipod Ampelisca abdita. Phase 1 TIEs were conducted using 10% and 40% dilutions of acutely toxic sediment. Gene expression was monitored in survivors and controls. An expression-based classifier was developed and evaluated against control organisms, organisms exposed to low or medium toxicity diluted sediment, and chemically selective manipulations of highly toxic sediment. The expression-based classifier correctly identified organisms exposed to toxic sediment even when little mortality was observed, suggesting enhanced sensitivity of the TIE process. The ability of the expression-based end point to correctly identify toxic sediment was lost concomitantly with acute toxicity when organic contaminants were removed. Taken together, this suggests that gene expression enhances the performance of the TIE process.
authors.affiliation: US EPA, National Exposure Research Laboratory AWBERC, MD 592 26 W. Martin Luther King Drive Cincinnati, Ohio 45268, United States. biales.adam@epa.gov
authors.forename: Adam D
authors.initials: AD
authors.lastname: Biales
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kostich
authors.forename: Robert M
authors.initials: RM
authors.lastname: Burgess
authors.forename: Kay T
authors.initials: KT
authors.lastname: Ho
authors.forename: David C
authors.initials: DC
authors.lastname: Bencic
authors.forename: Robert L
authors.initials: RL
authors.lastname: Flick
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Portis
authors.forename: Marguerite C
authors.initials: MC
authors.lastname: Pelletier
authors.forename: Monique M
authors.initials: MM
authors.lastname: Perron
authors.forename: Mark
authors.initials: M
authors.lastname: Reiss
mesh_terms: D033304:Amphipoda / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D059001:Aquatic Organisms / Q000187:drug effects / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D023381:Endpoint Determination; D005786:Gene Expression Regulation / Q000187:drug effects; D016678:Genome / Q000235:genetics*; D019015:Geologic Sediments / Q000737:chemistry; D012237:Rhode Island; D045483:Rivers / Q000737:chemistry; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D014874:Water Pollutants, Chemical