Some problems and errors in cytogenetic biodosimetry

Abstract

Human radiosensitivity is a quantitative trait that is generally subject to binomial distribution. Individual radiosensitivity, however, may deviate significantly from the mean (by 2-3 standard deviations). Thus, the same dose of radiation may result in different levels of genotoxic damage (commonly measured as chromosome aberration rates) in different individuals. There is significant genetic component in individual radiosensitivity. It is related to carriership of variant alleles of various single-nucleotide polymorphisms (most of these in genes coding for proteins functioning in DNA damage identification and repair); carriership of a different number of alleles producing cumulative effects; amplification of gene copies coding for proteins responsible for radioresistance, mobile genetic elements and others. Among the other factors influencing individual radioresistance are: the radioadaptive response; the bystander effect; the levels of endogenous substances with radioprotective and antimutagenic properties and environmental factors such as lifestyle and diet, physical activity, psychoemotional state, hormonal state, certain drugs, infections and others. These factors may have radioprotective or sensibilizing effects. Apparently, there are too many factors that may significantly modulate the biological effects of ionizing radiation. Thus, conventional methodologies for biodosimetry (specifically, cytogenetic methods) may produce significant errors if personal traits that may affect radioresistance are not accounted for.

Investigation of DNA Damage and Cell-Cycle Distribution in Human Peripheral Blood Lymphocytes under Exposure to High Doses of Proton Radiotherapy

“…Despite considerable progress in recent years, the precise mechanisms involved in the formation of rings versus acentric fragments remain a long-standing controversy in radiation cytogenetics. Ring chromosomes are usually formed as a result of two double-stranded DNA breaks from two terminal breaks in both chromosome arms, followed by linking of the broken ends; alternatively, ring chromosomes are formed from the joining of one broken chromosome end with the opposite telomere region [ 32 ]. The presence of rings causes mitotic instability, leading to cell death.…”

Further biodosimetry investigations using murine partial-body irradiation model

“…In the murine PBI model for biodosimetry evaluation, mice were immobilized by physical restraint during the irradiation. Stresses from various sources have the potential to confound the evaluation of radiation dose by biological methods (7) . Immobilization stress can alter the prooxidant-antioxidant balance and differed in radioresistant vs. radiosensitive rats (8) .…”