Modeling radiation injury-induced cell death and countermeasure drug responses in a human Gut-on-a-Chip

Cell Death Dis. 2018 Feb 14;9(2):223. doi: 10.1038/s41419-018-0304-8.


Studies on human intestinal injury induced by acute exposure to γ-radiation commonly rely on use of animal models because culture systems do not faithfully mimic human intestinal physiology. Here we used a human Gut-on-a-Chip (Gut Chip) microfluidic device lined by human intestinal epithelial cells and vascular endothelial cells to model radiation injury and assess the efficacy of radiation countermeasure drugs in vitro. Exposure of the Gut Chip to γ-radiation resulted in increased generation of reactive oxygen species, cytotoxicity, apoptosis, and DNA fragmentation, as well as villus blunting, disruption of tight junctions, and compromise of intestinal barrier integrity. In contrast, pre-treatment with a potential prophylactic radiation countermeasure drug, dimethyloxaloylglycine (DMOG), significantly suppressed all of these injury responses. Thus, the human Gut Chip may serve as an in vitro platform for studying radiation-induced cell death and associate gastrointestinal acute syndrome, in addition to screening of novel radio-protective medical countermeasure drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids, Dicarboxylic / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Caco-2 Cells
  • Cells, Cultured
  • DNA Fragmentation / drug effects
  • DNA Fragmentation / radiation effects
  • Gamma Rays / adverse effects*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / radiation effects
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / radiation effects
  • Lab-On-A-Chip Devices*
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / radiation effects
  • Models, Biological*
  • Permeability / drug effects
  • Permeability / radiation effects
  • Radiation Injuries / metabolism
  • Radiation Injuries / pathology
  • Radiation Injuries / prevention & control*
  • Radiation-Protective Agents / pharmacology*
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism
  • Tight Junctions / radiation effects


  • Amino Acids, Dicarboxylic
  • Radiation-Protective Agents
  • Reactive Oxygen Species
  • oxalylglycine