Distinct vascular genomic response of proton and gamma radiation-A pilot investigation

• Published in: PloS one 2019-02, Vol.14 (2), p.e0207503-e0207503
• Main Authors: Ricciotti, Emanuela, Sarantopoulou, Dimitra, Grant, Gregory R, Sanzari, Jenine K, Krigsfeld, Gabriel S, Kiliti, Amber J, Kennedy, Ann R, Grosser, Tilo
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Aorta; Aorta - radiation effects; Apoptosis; Apoptosis - genetics; Apoptosis - radiation effects; Atherosclerosis; Biology and Life Sciences; Blood; Breast cancer; Cancer therapies; Cardiovascular diseases; Cell cycle; Cellular stress response; Comparative analysis; Coronary vessels; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - genetics; DNA Damage - radiation effects; Dose-response effects; Dose-response relationship; Dose-Response Relationship, Radiation; Dosimetry; Drug dosages; Gamma irradiation; Gamma Rays; Gene expression; Gene sequencing; Genes; Genetic research; Genome - genetics; Genome - radiation effects; Genomics - methods; Health aspects; Health risks; Heart attacks; Inflammation; Inflammation - genetics; Investigations; Ionizing radiation; Irradiation; Kinases; Male; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Oncology; Pharmacology; Physical Sciences; Pilot Projects; Proton irradiation; Protons; Radiation; Radiation (Physics); Radiation damage; Radiation effects; Radiation therapy; Radiation, Ionizing; Radiotherapy; Ribonucleic acid; RNA; RNA sequencing; Trend analysis; γ Radiation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0207503

The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge. We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5-200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response. While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes; q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation; p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships. Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.