Research ArticleRadiation Toxicity

PHD Inhibition Mitigates and Protects Against Radiation-Induced Gastrointestinal Toxicity via HIF2

Science Translational Medicine  14 May 2014:
Vol. 6, Issue 236, pp. 236ra64
DOI: 10.1126/scitranslmed.3008523

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Going with the Gut for Radiation Protection

Radiation is a valuable adjunct to cancer therapy, but it also causes many side effects that limit the doses patients can tolerate. Accidental exposure is a less common source of radiation but one that is widely feared because of the lack of control over dose and timing and the resulting potential for severe side effects or death. The bone marrow toxicity of radiation can be mitigated with a bone marrow transplant, but there are no approved treatments for another lethal effect of radiation, gastrointestinal toxicity.

Here, Taniguchi and colleagues present the radioprotective effects of a small-molecule, dimethyloxallyl glycine (DMOG), an inhibitor of prolyl hydroxylases. The authors demonstrate that mice treated with DMOG are protected from gastrointestinal damage and survive otherwise lethal amounts of irradiation to the abdomen. The protective effects of DMOG are observed even when it is given up to 24 hours after exposure to the lethal doses of radiation, which makes it a promising candidate for treatment of unplanned radiation exposures.

The current study is in mice, and the effectiveness and safety of DMOG will have to be confirmed in humans before this drug can be used in the clinical setting. However, even if DMOG itself turns out to be unsuitable for human use, the understanding of its mechanism and the knowledge that targeting prolyl hydroxylases can mitigate radiation toxicity will be invaluable for developing future treatments to protect human patients from radiation.