Impact on the Transcriptome of Proton Beam Irradiation Targeted at Healthy Cardiac Tissue of Mice.

Simple Summary: The nature of different types of ionizing radiation is central to the modality of affecting biological targets. The main data library on radiotherapy effects we can access is on photon sources, and any other type of radiation is compared to that, not always considering that different physical features might contribute in quite different ways to the quality of visible effects. A large body of study already supports this vision, but a lot of work is still to be done, particularly on irradiated healthy tissue in the vicinity of the cancer target. This study aims to gain information on the effects of anti-cancer therapeutic protons as a function of radiation dose and time post-irradiation on healthy cardiac tissue through the analysis of transcriptionally activated genes and relative molecular pathways. Proton beam therapy is considered a step forward with respect to electromagnetic radiation, thanks to the reduction in the dose delivered. Among unwanted effects to healthy tissue, cardiovascular complications are a known long-term radiotherapy complication. The transcriptional response of cardiac tissue from xenografted BALB/c nude mice obtained at 3 and 10 days after proton irradiation covering both the tumor region and the underlying healthy tissue was analyzed as a function of dose and time. Three doses were used: 2 Gy, 6 Gy, and 9 Gy. The intermediate dose had caused the greatest impact at 3 days after irradiation: at 2 Gy, 219 genes were differently expressed, many of them represented by zinc finger proteins; at 6 Gy, there were 1109, with a predominance of genes involved in energy metabolism and responses to stimuli; and at 9 Gy, there were 105, mainly represented by zinc finger proteins and molecules involved in the regulation of cardiac function. After 10 days, no significant effects were detected, suggesting that cellular repair mechanisms had defused the potential alterations in gene expression. The nonlinear dose–response curve indicates a need to update the models built on photons to improve accuracy in health risk prediction. Our data also suggest a possible role for zinc finger protein genes as markers of proton therapy efficacy. [ABSTRACT FROM AUTHOR]