Abstract
Compared to low doses of gamma irradiation (γ-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. Three- to four-month-old female CB6F1/Hsd mice were exposed once to one of four different doses of the following types of radiation: γ-IR 137Cs (40-160 cGy, 0.662 MeV), 14Si-IR (4-32 cGy, 260 MeV/n), or 22Ti-IR (3-26 cGy, 1 GeV/n). At 16 months post-exposure, animals were sacrificed and hearts were harvested and archived as part of the NASA Space Radiation Tissue Sharing Forum. These heart tissue samples were used in our study for RNA isolation and microarray hybridization. Functional annotation of twofold up/down differentially expressed genes (DEGs) and bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common DEGs across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in 14Si- and 22Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs. Thus, our study may provide experimental evidence of excess relative risk (ERR) quantification of low/very low doses of full-body space-type IR-associated degenerative disease development.
Highlights
During future exploration-type space missions, astronauts could be exposed to doses of space-type radiation (IR) (~0.4–0.5 Gy) from galactic cosmic rays (GCR), especially during Mars missions, where astronauts would not have access to comprehensive health care services for at least 2–3 years [1,2]
Our results show that 16 months after a single low- or very low dose IR exposure, the gene expression in the heart tissue is significantly differentially regulated compared to the sham-treated, non-irradiated controls, suggesting there are long-term effects on dysregulation of varying molecular pathways that are associated with various degrees of CV, pulmonary, and metabolic diseases, as well as biological processes, including abnormal circadian rhythms, cancer, Hutchinson–Gilford progeria syndrome, etc
We found that basic helix-loop-helix family member E41 (Bhlhe41), cyclindependent kinase inhibitor 1A (Cdkn1a), Slc41A3, and aryl hydrocarbon receptor nuclear translocator like (Arntl) were all significantly upregulated after 137 Cs-IR exposure in a dose–response manner
Summary
During future exploration-type space missions, astronauts could be exposed to doses of space-type radiation (IR) (~0.4–0.5 Gy) from galactic cosmic rays (GCR), especially during Mars missions, where astronauts would not have access to comprehensive health care services for at least 2–3 years [1,2]. Our results show that 16 months after a single low- or very low dose IR exposure, the gene expression in the heart tissue is significantly differentially regulated compared to the sham-treated, non-irradiated controls, suggesting there are long-term effects on dysregulation of varying molecular pathways that are associated with various degrees of CV, pulmonary, and metabolic diseases, as well as biological processes, including abnormal circadian rhythms, cancer, Hutchinson–Gilford progeria syndrome, etc. Our study may provide additional experimental evidence of the level of gene expression for estimation of excess relative risk (ERR) for the development of CV and other diseases due to exposure to low or very low doses of whole-body space-type IR
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