Distinct vascular genomic effects of proton and gamma radiation
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ABSTRACT:
PROVIDER: PRJNA415173 | ENA |
REPOSITORIES: ENA
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Project description:We performed comparative RNA sequencing of the early (4 hrs) dose response (0.5 – 200 cGy whole body dose, 10 dose levels) of the mouse aorta to proton and gamma radiation. Total-body proton radiation of conscious animals was performed using a proton beam produced by a cyclotron system, while total-body gamma radiation of animals was performed using a Caesium-137 gamma source. A trend analysis identified genes that showed a dose response, using data permutation to estimate a false discovery rate (q-value) for each gene. We identified 29 and 194 genes (q-value ≤ 0.1) that were upregulated with increasing doses of proton and gamma radiation, respectively. No genes were down-regulated. While fewer genes were dose-responsive to proton radiation, the magnitude of the effect was greater than with gamma radiation. These highly responsive genes were enriched for pathways involved in the response to DNA damage, apoptosis, cellular stress and inflammation (p < 0.01). Gamma radiation responsive genes included the same pathways, but extended to genes in vasculature specific pathways. Genes responsive to both radiation types (19 genes at q-value ≤ 0.1) showed almost perfectly superimposable dose-response relationships. We observed the same superimposable dose response relationship of gamma and proton radiations in a subset of genes validated by quantitative PCR not only in the aorta but also in liver, lung, heart and kidney. Despite a relative similar relative biological effectiveness of protons and gamma photons and the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response. It seems plausible that these genomic differences translate into differences in the biological processes leading to cardiovascular pathologies.
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