Synergistic effect of high charge and energy particle radiation and chronological age on biomarkers of oxidative stress and tissue degeneration: a ground-based study using the vertebrate laboratory model organism Oryzias latipes.
High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZE particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration.
Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, Georgia, United States of America; Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, China.
Xuan
X
Zheng
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Xinyan
X
Zhang
Department of Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, China.
Lingling
L
Ding
Department of Pathology, Georgia Regents University, Augusta, Georgia, United States of America.
Jeffrey R
JR
Lee
Department of Otolaryngology and Center for Biotechnology & Genomic Medicine, Georgia Regents University, Augusta, Georgia, United States of America.
Paul M
PM
Weinberger
Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, Georgia, United States of America; Departments of Radiation Oncology and Biochemistry, Emory University, Atlanta, Georgia, United States of America.
William S
WS
Dynan
D000375:Aging / Q000528:radiation effects*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003359:Cosmic Radiation; D015227:Lipid Peroxidation / Q000528:radiation effects; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D009990:Oryzias; D018384:Oxidative Stress / Q000528:radiation effects*; D013026:Space Flight
D015415:Biomarkers