Long terms effects of very low dose particle radiation on the gene expression in the mouse heart

We sought to determine the long-term effects of radiation (IR) on gene expression in the whole heart as a function of IR type and dose. We hypothesize that compared to low doses of gamma-IR, high charge and energy (HZE) particle-IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type- and dose-dependent. We provide for the first time the transcriptome analysis of mouse hearts exposed to low and very low doses of gamma- (137Cs), silicon- (14Si), and titanium- (22Ti) irradiation. Our results show that 16 months after low and very low dose IR exposure, the gene expression in the heart tissue is significantly differentially regulated, suggesting there are long-term effects on dysregulation of varying molecular pathways that are associ-ated with various degrees of cardiovascular, pulmonary and metabolic diseases, as well as biological processes, including abnormal circadian rhythm, cancer, Hutchinson-Gilford progeria syndrome, etc. 72 female CB6F1/Hsd mice were irradiated with a single, full-body HZE dose (≤0.5 Gy) of 260 MeV/n silicon (14Si, LET ~ 70 keV/µm) and 1,000 MeV/n titanium (22Ti, LET ~ 100 keV/µm) Another group of animals were also irradiated with 137Cs gamma-ray that served as a low-LET reference. Control sham-treated animals were placed in clear plastic holders for equivalent exposure times but were not irradiated. Animals were eutanazied 16 months after a single dose of full-body IR with the corresponding ions and doses. Total RNA was isolated with total RNA isolation kit from heart organs (n=4-5 per group) according to manufacturer’s instructions. Gene expression profiling was performed using Affymetrix Clariom S Mouse Array according to the manufacturer’s instructions (Affymetrix, Inc., Santa Clara, CA). Chips were scanned with an Affymetrix GeneChip Scanner using 3000 Command Console Software. Signal intensities were converted to log2 RMA expresson values.