Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

Abstract

The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.

Cancer Studies under Space Conditions: Finding Answers Abroad

“…However, the problem with these countermeasures is that all of them have been studied in a high-dose radiation environment, making them unproven to work in a low-dose environment, such as space [ 109 ]. A more detailed discussion can be found elsewhere [ 110 ].…”

Biological Mechanisms to Reduce Radioresistance and Increase the Efficacy of Radiotherapy: State of the Art

“…In addition to direct DNA damage, originating from the physical interaction between IR and the DNA helix, water radiolysis occurs in irradiated cells, and the reactive oxygen species (ROS) produced give rise to oxidative stress and DNA damage generation [ 4 , 5 ] that contribute to the cytotoxic effects of IR [ 6 ]. Oxidative DNA damage consists of oxidized bases such as 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), oxidized pyrimidine derivatives (i.e., thymine glycol and 5,6 dihydrouracil), oxidized base-derived apurinic/apyrimidinic sites and SSBs [ 7 ]. According to the nature of IR-induced DNA damage, different pathways come into play to repair the lesion and restore cell functionality.…”

Editorial to the Special Issue: “Dysregulation of Human Molecular and Metabolic Mechanisms Resulting in Oxidative Stress and Damage Generation in the Space Environment”

“…To address multiple OSaD factors in chorus with one another, the choice of research model is critical and certainly the likelihood that multiple models may need to be employed is warranted. The current scientific literature documents have extensively employed rodent and human physiological platforms to evaluate OSaD generated toxic effects, spanning many different physiological and analytical subsystem models [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

“…Klein et al in 2021 and Krishnan et al in 2021 described how even low dose neutron radiation through the generation of RONS damages the normal operation of the CNS and that chronic low dose exposure negatively effects the hippocampus and the prefrontal cortex, due to altered neurotransmission [ 14 , 15 ]. These studies illuminate the disruption of cellular processes at the DNA and molecular genetic levels [ 15 , 16 , 17 ]. The central flaw in the previous work of the space radiation community at large was the amount and manner of administration of radiation in acute protocols used in the attempts to mimic actual GCR.…”