Metabolomic Analysis of the Secretome of Human Embryonic Stem Cells Following Methyl Parathion and Methyl Paraoxon Exposure, Phase 1: Initial Nontargeted LC-MS.

摘要

Current literature suggests diverse toxicological consequences for methyl parathion (MP) and its active metabolite, methyl paraoxon (MPO) exposure. These studies, however, have been based on either human epidemiological studies, in vivo animal studies, or in vitro studies using immortal cell lines. Currently, there remains no definitive connection to the molecular events that occur during MP and MPO exposure in normal human cells. Furthermore, chemicals that have certain known effects in adults can have dramatically different toxic effects during embryonic and prenatal development. Since undifferentiated human embryonic stem cells (hESC) maintain the ability to differentiate into any somatic cell in the body, they provide a unique window into the influence of toxicants on the entire early human development. The purpose of this study was to perform initial nontargeted metabolomic analysis on hESC exposed to MP and MPO to identify human metabolites and metabolic pathways which are perturbed following exposure to these chemicals. From this study, two main conclusions were reached: (1) hESC are not able to metabolize MP into MPO, and (2) MPO is much more disruptive to key developmental metabolic pathways at physiologically relevant concentrations than is MP.