Arsenic Toxicology: Translating between Experimental Models and Human Pathology

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 pheno-typic anchoring as a means to unify experimental observations and disease outcomes. Objectives: We examined the use of pheno-typic anchors to translate experimental data to human pathology and investigated research needs for which pheno-typic anchors need to be developed. Methods: During a workshop, we discussed experimental systems investigating arsenic dose/exposure and pheno-typic 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 pheno-typic anchoring of experimental results to pathologies from specific human exposures. Discussion: Disease outcome is likely dependent on cell-type-specific responses and inter-action with individual genetics, other toxicants, and infectious agents. Potential pheno-typic 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.