Study On The Synergistic Biological Effects Of Space Radiation And Microgravity By Using Spaceflown C.Elegans

The mechanism of human physical dysfunctions induced by space radiations and microgravity, which are recognized as unique spaceflight environments, is considered as the frontier issues in space biology. However, it is undetermined that whether there is synergistic effects between space radiations and microgravity. To address the potential synergistic effects and its mechanism on an individual level between microgravity and space radiations, wild type and dys-1 and ced-1 mutants of Caenorhabditis elegans were treated by static slot (μg, space radiation),1-g centrifugal slot (1g, space radiation) within a BIOBOX and ground control slot during the Shenzhou-8 space mission. After 16.5 days of spaceflight, approximately 2000 worms endured space synergistic environment and space radiation environment from each group were collected for transcriptome analyses (mRNA and miRNA microarrays). These data were performed enrichment analyses by distribution characteristics, biological processes, and signal pathways, with particular attention given to DNA damage response (DDR) processes.The results show that, twice as many genes significantly altered in the spaceflight synergistic environment than space radiations alone in wild-type C. elegans, and thus, spaceflight synergistic environment stress resulted in gene expression changes that were related to regulating protein phosphorylation/dephosphorylation, histone metabolism, DNA repair pathway, and signal transduction pathways, whereas spaceflight radiation stress affected the expression of metabolism-, growth-, and development-related genes. However, these changes were reduced in the gravity-sensing defective dys-1 mutants, and the dys-1 mutants mainly promoted the pathways of lipid, amino acid, and carbohydrate metabolism transcriptionally. Compared to wild type worm, the ced-1 mutant was detected to promote genes involving in protein phosphorylation/dephosphorylation in both space conditions, while extracellular matrix organization and DNA repair pathways were additionally affected under the space synergistic environment, and AKT-related signal transduction under space radiation environment, thus, the radiation-sensing mutant ced-1 had an enhanced radiation response. DDR-related genes expression profiling showed that microgravity probably regulated more DDR-related genes by activating signal sensing, transduction and execution of DDR process. Affected by ced-1 mutant, C.elegans activated more genes involving DNA repair and apoptosis in response to space synergistic environment. Additionally, miR-124, miR-80 families, etc. were predicated to play roles in DDR.Our results suggest that microgravity, as the main stress factor encountering during short-duration spaceflight, together with space radiation can affect various biological networks and DDR processes in C. elegans, and that this is dependent on the gravity-signal pathways. These findings will be relevant for future assessments of human health risks and protection against space environments.