Heavy ion space radiation triggers ongoing DNA base damage by downregulating DNA repair pathways

Long-duration space missions outside low earth orbit will expose astronauts to a cumulative dose of high-energy particle radiation especially to highly damaging heavy ion radiation, which poses considerable risk to astronauts' health. The purpose of the current study was to quantitatively identify oxidatively induced DNA base modifications and assess status of the repair pathways involved in removing the modified bases in mouse intestinal cells after exposure to γ-rays and iron radiation. Mice (C57BL/6J; 6 to 8 weeks; female) were exposed to 0.5 Gy of either γ-rays or iron radiation and control mice were sham-irradiated. Intestinal tissues were collected 2 months after radiation. DNA base lesions were measured using gas chromatography-tandem mass spectrometry with isotope‑dilution. Base excision repair (BER) and nucleotide excision repair (NER) pathways were assessed using PCR and immunoblotting. Effects of iron radiation were compared to γ-rays and sham-irradiated controls. Exposure to iron radiation resulted in significantly higher levels of several DNA base lesions relative to control animals and those exposed to γ radiation. Assessment of BER and NER showed downregulation of pathway factors both at the RNA as well as at the protein levels. Our results not only provide important insight into DNA damage pattern in intestinal cells in response to iron radiation, but they also confirm our previous immunohistochemistry data on oxidatively induced DNA damage. We suggest that downregulation of the BER and NER pathways is contributing to ongoing DNA base damages long time after radiation exposure and has implications for chronic diseases including gastrointestinal diseases after heavy ion radiation exposure during space travel.