Inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation: comparison of the dicentric and micronucleus assays

Abstract

Ionizing radiation can induce a wide range of DNA damage that leads to chromosomal aberrations. Some of those aberrations (dicentrics and micronuclei) are applied in biodosimetry. Biological dosimetry assumes similar radiosensitivity of each donor, but it does not exclude inter-individual variations in radiation susceptibility. Therefore, for biological reasons, it is always challenging to investigate inter-individual variability in response to radiation. For mechanistic reasons, it is also interesting to investigate the correlation between dicentric and micronuclei formation in response to radiation. In this experiment, irradiated blood specimens from 14 healthy male and female donors have been used to evaluate inter-individual variability in response to the genotoxic effects of X-ray radiation, as well as the dose-response relationship and test sensitivity using two endpoints (dicentrics and micronuclei). The results showed similar patterns of cytogenetic biomarker distribution between donors, but differences in the response of some donors at some doses. Data also showed that responses of male donors were better detected using the dicentric test, while for females, micronucleus frequencies were higher in response to the same dose of radiation. No influence of smoking status or age on specific responses was observed. Group variability in response to radiation was evaluated using coefficient of variation for each group of individuals irradiated with the same doses; as the dose increases, group variability becomes substantially lower. Despite sporadic inter-individual variability, trend of radiation-induced changes was similar. Produced calibration curves for both types of damage revealed dicentrics as genetic damage more typical for radiation than micronuclei.

Radiation-Induced Chromosomal Aberrations and Immunotherapy: Micronuclei, Cytosolic DNA, and Interferon-Production Pathway

“…With FISH-painting, it became possible to look at stable CA and, therefore, to perform retrospective biodosimetry. Inter-individual variability in measurements of radiation-induced CA in PBL ( 7 ) has triggered many efforts to investigate ex vivo measurements as predictive assays of individual susceptibility to radiation therapy. Despite these high expectations, the results have been disappointing, since no clear correlation with individual toxicity could be established ( 8 , 9 ).…”

Rate of individuals with clearly increased radiosensitivity rise with age both in healthy individuals and in cancer patients

“…A study comparing radiosensitivity of ten new borns using umbilical cord blood compared with twenty adults did not find an increase with age, but a distinct higher radiosensitivity of newborns [ 37 ]. Similar in a group of 14 individuals no influence of age on dicentric aberrations was found [ 38 ]. In a breast cancer cohort of 100 patients age at onset of disease did not correlate with radiosensitivity [ 39 ].…”

Single nucleotide polymorphisms in ATM, TNF-α and IL6 genes and risk of radiotoxicity in breast cancer patients

“…Initially, individual radiosensitivity was studied through cytogenetic and cellular tests such as the comet assay, G2 and cell survival and their combination [20,21,22,23]. However, none of these methods has been validated in a clinical setting.…”