Cytogenetic effects of low-dose radiation with different LET in human peripheral blood lymphocytes

Abstract

Chromosome damage and the spectrum of aberrations induced by low doses of gamma-irradiation, X-rays and accelerated carbon ions (195 MeV/u, LET 16.6 keV/microm) in peripheral blood lymphocytes of four donors were studied. G0-lymphocytes were exposed to 1-100 cGy, stimulated by PHA, and analyzed for chromosome aberrations at 48 h post-irradiation by the metaphase method. A complex nonlinear dose-effect dependence was observed over the range of 1 to 50 cGy. At 1-7 cGy, the cells showed the highest radiosensitivity per unit dose (hypersensitivity, HRS), which was mainly due to chromatid-type aberration. According to the classical theory of aberration formation, chromatid-type aberrations should not be induced by irradiation of unstimulated lymphocytes. With increasing dose, the frequency of aberrations decreased significantly, and in some cases it even reached the control level. At above 50 cGy the dose-effect curves became linear. In this dose range, the frequency of chromatid aberrations remained at a low constant level, while the chromosome-type aberrations increased linearly with dose. The high yield of chromatid-type aberrations observed in our experiments at low doses confirms the idea that the molecular mechanisms which underlie the HRS phenotype may differ from the classical mechanisms of radiation-induced aberration formation. The data presented, as well as recent literature data on bystander effects and genetic instability expressed as chromatid-type aberrations on a chromosomal level, are discussed with respect to possible common mechanisms underlying all low-dose phenomena.

ATM-Dependent Hyper-Radiosensitivity in Mammalian Cells Irradiated by Heavy Ions

“…Russian researchers found that the HRS/IRR could be observed by the anaphase method and micronucleus assay in X-ray using Chinese hamster V79 cells and human melanoma cells (27). Recently, they prompted a complex nonlinear dose-effect dependence in chromosome aberrations over the dose range of 1-50 cGy with different LETs in human peripheral blood lymphocytes, high yield of chromatid type aberrations was found at HRS dose range in both low and high LET radiations, which confirmed the idea that the molecular mechanisms that underlie the HRS phenotype may differ from the classical mechanisms of radiation-induced aberration formation, they proposed that there were possibly common mechanisms underlying all low-dose phenomena (2). Our data supported that there was the occurrence of HRS/IRR for HPRT mutation frequency in GM cells exposed to carbon ions (Fig.…”

“…Although the intrinsic mechanisms and targets of low-dose effects are not fully clear, large amount of data indicate that below 0.5 Gy, certain effects are not quantitatively related to the dose and that fundamentally different processes are involved in the cells' response to ionizing radiation (1)(2)(3).…”

Differential Molecular Stress Responses to Low Compared to High Doses of Ionizing Radiation in Normal Human Fibroblasts

“…Indeed, numerous reports confirmed the lack of linearity in radiation dose responses at low doses for such end points as micronuclei ( Słonina et al . 2006 ), chromosomal aberrations ( Nasonova et al . 2006 ), cellular clonogenic survival ( Marples and Joiner 1993 ) and others.…”

Comparison between two FISH techniques in the in vitro study of cytogenetic markers for low-dose X-ray exposure in human primary fibroblasts

“…It could be attributable to the fact that the system responded to the X-rays with an excess of damage for the doses 0.1 and 0.25 Gy, recalling a possibility of a kind of low-dose HRS, and actually such an occurrence has been reported with classical non-molecular cytogenetic techniques on rodent and human cells (Tsoulou et al, 2001; Nasonova et al, 2006). Nevertheless the regression functions without low-dose HRS-like correction were preferred because without further experimental points far from HRS peak a conclusive evidence is missing, and secondly for practical reasons of calculation of the thresholds doses for the detectable damage induction.…”