title: Arsenic toxicology: translating between experimental models and human pathology.
abstract: BACKGROUND
  Chronic arsenic exposure is a worldwide health problem. How arsenic exposure promotes a variety of diseases is poorly understood, and specific relationships between experimental and human exposures are not established. We propose phenotypic anchoring as a means to unify experimental observations and disease outcomes.
  
  
  OBJECTIVE
  We examined the use of phenotypic anchors to translate experimental data to human pathology and investigated research needs for which phenotypic anchors need to be developed.
  
  
  METHODS
  During a workshop, we discussed experimental systems investigating arsenic dose/exposure and phenotypic expression relationships and human disease responses to chronic arsenic exposure and identified knowledge gaps. In a literature review, we identified areas where data exist to support phenotypic anchoring of experimental results to pathologies from specific human exposures.
  
  
  CONCLUSIONS
  Disease outcome is likely dependent on cell-type-specific responses and interaction with individual genetics, other toxicants, and infectious agents. Potential phenotypic anchors include target tissue dosimetry, gene expression and epigenetic profiles, and tissue biomarkers.
  
  
  CONCLUSIONS
  Translation to human populations requires more extensive profiling of human samples along with high-quality dosimetry. Anchoring results by gene expression and epigenetic profiling has great promise for data unification. Genetic predisposition of individuals affects disease outcome. Interactions with infectious agents, particularly viruses, may explain some species-specific differences between human pathologies and experimental animal pathologies. Invertebrate systems amenable to genetic manipulation offer potential for elaborating impacts of specific biochemical pathways. Anchoring experimental results to specific human exposures will accelerate understanding of mechanisms of arsenic-induced human disease.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA. jcstates@louisville.edu
authors.forename: J Christopher
authors.initials: JC
authors.lastname: States
authors.forename: Aaron
authors.initials: A
authors.lastname: Barchowsky
authors.forename: Iain L
authors.initials: IL
authors.lastname: Cartwright
authors.forename: John F
authors.initials: JF
authors.lastname: Reichard
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Futscher
authors.forename: R Clark
authors.initials: RC
authors.lastname: Lantz
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D011247:Pregnancy
chemical_list: D001151:Arsenic