Human individual radiation sensitivity and prospects for prediction

Abstract

In the past few decades, it has become increasingly evident that sensitivity to ionising radiation is variable. This is true for tissue reactions (deterministic effects) after high doses of radiation, for stochastic effects following moderate and possibly low doses, and conceivably also for non-cancer effects such as cardiovascular disease, the causal pathway(s) of which are not yet fully understood. A high sensitivity to deterministic effects is not necessarily correlated with a high sensitivity to stochastic effects. The concept of individual sensitivity to high and low doses of radiation has long been supported by data from patients with certain rare hereditary conditions. However, these syndromes only affect a small proportion of the general population. More relevant to the majority of the population is the notion that some part of the genetic contribution defining radiation sensitivity may follow a polygenic model, which predicts elevated risk resulting from the inheritance of many low-penetrance risk-modulating alleles. Can the different forms of individual radiation sensitivities be inferred from the reaction of cells exposed ex vivo to ionising radiation? Can they be inferred from analyses of individual genotypes? This paper reviews current evidence from studies of late adverse tissue reactions after radiotherapy in potentially sensitive groups, including data from functional assays, candidate gene approaches, and genome-wide association studies. It focuses on studies published in 2013 or later because a comprehensive review of earlier studies was published previously in a report by the UK Advisory Group on Ionising Radiation.

Biological effectiveness of very high gamma dose rate and its implication for radiological protection

“…Experiments were carried out with two cell systems: human peripheral blood mononuclear cells (PBMC) and U2OS-53BP1 cells. The reason for choosing PBMC was that they are extensively used for the purpose of retrospective biological dosimetry (Wojcik et al 2017 ) and for testing biomarkers of individual radiosensitivity (Rajaraman et al 2018 ). The reason for choosing U2OS-53BP1 cells was that they constitutively express the 53BP1 protein, allowing analysis of ionising radiation-induced repair foci (IRIF) (Sollazzo et al 2017 ) without antibody labelling.…”

Post-irradiation Hyperamylasemia Is a Prognostic Marker for Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Pediatric Population: a Retrospective Single-centre Cohort Analysis.

“…Human response to radiation is widely different due to individual cellular radiosensitivity, primarily determined by genetic factors [28,29]. However, the molecular basis of individual radiosensitivity remains poorly understood [30].…”

Understanding the Effects of Deep Space Radiation on Nervous System: The Role of Genetically Tractable Experimental Models

“…Without major technological leaps in shielding strategies [6], intrinsic or induced biological resilience to space radiation chronic exposure will probably be among the crucial factors to decide about risk acceptability. Individual sensitivity to acute or chronic exposure to radiation is dependent on genetic background [7]. Following recent developments in sequencing technologies, determination of individual genomes and acquisition of multi-omic information on individuals' biological samples has become a relatively low-cost routine.…”

“…In theory, these resources could allow for the screening of many crew candidates, to identify those possessing particularly sensitive or resistant biological backgrounds. However, our knowledge of the genetic and biological traits associated with sensitivity to space radiation is still very limited [7]. NASA has underscored four risks that may imply important health concerns for astronauts: acute radiation syndrome, carcinogenesis, degenerative tissue alterations, and central nervous system (CNS) loss of performance [3].…”