Epichlorohydrin‐Induced DNA‐Protein Cross‐Links in Human Leukemia Cells

Over 1.5 million tons of epichlorohydrin (ECH) are used annually in the manufacturing of epoxy resins and polymers. A probable human carcinogen, ECH shares structural homology to nitrogen mustards, the oldest class of anti‐tumor drugs. Such bifunctional alkylating agents can react with DNA and proteins, leading to genotoxic effects. Previous work in our lab has shown that treating human leukemia (HL‐60) cells with toxic doses of ECH leads to the formation of cross‐links and triggers apoptosis. In these studies, cross‐linking was quantified via single cell gel electrophoresis (the comet assay), which does not distinguish between DNA‐DNA cross‐links and DNA‐protein cross‐links (DPCs). The goal of this work is to further characterize ECH‐induced DPCs. Nuclear proteins that bind to biotinylated DNA after treating HL‐60 cells with ECH under different conditions are captured via streptavidin beads. Cross‐linked proteins are then characterized through gel electrophoresis. Preliminary data suggest that ECH does induce DPC formation, with greater cross‐linking efficiency at higher concentrations of ECH. Our findings could have significance for understanding the occupational risks of ECH exposure among industrial workers.Support or Funding InformationSupported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM0103423.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.