PT  - JOURNAL ARTICLE
AU  - Ricciotti Emanuela
AU  - Dimitra Sarantopoulou
AU  - Gregory R. Grant
AU  - Jenine K. Sanzari
AU  - Gabriel S. Krigsfeld
AU  - Amber J. Kiliti
AU  - Ann R. Kennedy
AU  - Tilo Grosser
TI  - Distinct vascular genomic response of proton and gamma radiation
AID  - 10.1101/460766
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 460766
4099  - http://biorxiv.org/content/early/2018/11/02/460766.short
4100  - http://biorxiv.org/content/early/2018/11/02/460766.full
AB  - Purpose. 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.Materials and methods. 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.Results. 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.Conclusions. 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.