Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

Abstract

Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

A priming dose of protons alters the early cardiac cellular and molecular response to 56 Fe irradiation

“…Due to experimental set-up and limited availability of tissues, we did not have the opportunity to include other time points or assess cardiac function or histology. However, previous research in a similar mouse model of exposure to protons (0.5 Gy, 1 GeV) and 56 Fe (0.15 Gy, 1 GeV/n) showed long-term alterations in cardiac function and structure in response to these charged particles [13-15]. …”

“…Similar to our results, recent work on tissue samples of lung [34] and brain (Antiño Allen, PhD, personal communication) of mouse models showed that protons followed at 24 hours by 56 Fe resulted in molecular and functional alterations that were significantly different when compared to either source of radiation alone. Moreover, in mice that were challenged with an acute myocardial infarction, prior proton irradiation increased the expression of pro-survival genes, improved the restoration of cardiac function, and enhanced the process of cardiac remodeling when examined from hours to months after irradiation [13]. Our work confirms these earlier findings and demonstrates that the molecular and cellular response of the heart can be modified by a priming dose of protons at lower energy levels (150 MeV) than in the previous report by Yan et al (1 GeV).…”

“…Exposure to protons (0.5 Gy, 1 GeV) and 56 Fe (0.15 Gy, 1 GeV/n) in a mouse model induced cardiac infiltration of CD68-positive cells, increased DNA oxidation, myocardial fibrosis, and modified cardiac function, both at baseline and in response to myocardial infarction, in a radiation-type specific manner [13-15]. Moreover, exposure to 28 Si (0.1-0.5 Gy, 300 MeV/n) caused prolonged apoptosis and increased expression of the common pro-inflammatory cytokines interleukin (IL)-1β, IL-6, or tumor necrosis factor (TNF)-α in a mouse model [16].…”

Sperm quality and DNA damage in men from Jilin Province, China, who are occupationally exposed to ionizing radiation

“…In addition to high doses of radiation, low-dose ionizing radiation (LDIR) might increase the risk of cardiovascular disease, lens opacity, and some other noncancerous diseases (Hammer et al, 2013;Kamiya et al, 2015;Kreuzer et al, 2015). The authors of previous research have reported that cardiovascular morbidity and mortality may occur decades after ionizing radiation exposure (Yan et al, 2014). The health risks arising from exposure to low doses of ionizing radiation should be re-evaluated (El-Saghire et al, 2013).…”

Metabolomic Profiling of Urine Samples from Mice Exposed to Protons Reveals Radiation Quality and Dose Specific Differences

“…One of the primary concerns for space travel is exposure to space radiation. Radiation exposure and more significantly space radiation have been connected with increased carcinogenesis, cataract development, neurological health risks of the central nervous system and cardiovascular disease, as well as with short-term adverse effects that could compromise mission success (1–6). Radiation can also leads to perturbations of metabolic processes and inflammatory processes, and these changes can be reflected in biofluids, such as urine and blood, that could provide a snap shot of an individual’s current physiological state.…”