scholarly journals Influence of Polymorphisms of DNA Repair and GST Genes on Genotoxic Damage and Mutagen Sensitivity in Workers Occupationally Exposed to Very Low Doses of Ionizing Radiation

2019 ◽  
Vol 9 (23) ◽  
pp. 5175 ◽  
Author(s):  
Stufano ◽  
Chiarappa ◽  
Bagnulo ◽  
Drago ◽  
Rapisarda ◽  
...  

The study investigated the influence of genetic polymorphisms of the enzymes for DNA repair and detoxification of reactive intermediates on spontaneous and bleomycin-induced (BLM) genotoxic damage in 43 workers exposed to very low doses of ionizing radiation (IR) (mean cumulative dose 5.31 mSv) and 43 subjects with no occupational exposure to IR (controls). In all the subjects examined, the frequency of chromosome aberrations (CAs) and micronuclei (MN), both spontaneous and BLM-induced, the Comet assay parameters (tail intensity), the genotypic variants of the DNA repair enzymes XRCC1 (Arg194Trp, Arg280His, Arg399Gln), XRCC3 (Thr241Met), XPD (Lys751Gln), and of the detoxification enzymes GSTM1 and GSTT1 (null genotype) and BLMH (A1450G) were determined. Among the biomarkers considered, only the frequency of total CAs (p < 0.05), and in particular of chromosome breaks (p < 0.01), was found to be significantly higher in the exposed workers than the controls. The frequency of spontaneous MN was higher in subjects with at least one allelic variant in XRCC1 than in carriers of the wild-type, but again only in exposed workers (p = 0.046). Linear regression analysis showed a positive dependency of the frequency of spontaneous chromosome breaks on occupational exposure, and a dependency of the frequency of BLM-induced MN negative on occupational exposure and positive on alcohol consumption and the null GSTM1 genotype. In conclusion, the frequency of chromosome breaks seems to be a useful cytogenetic biomarker for exposure to very low doses of IR, while only the combined effect of different gene variants or genetic, occupational, and lifestyle habits factors seems to be able to modulate the genotoxic effect of very low doses of IR.

Author(s):  
Ronald Gerard Silva ◽  
Marcus Vinícius Oliveira Barros Alencar ◽  
Jadson Silva Teixeira ◽  
Reyca Rodrigues e Silva ◽  
Márcia Fernanda Correia Jardim Paz ◽  
...  

1998 ◽  
Vol 45 (2) ◽  
pp. 605-610 ◽  
Author(s):  
J Palus ◽  
E Dziubałtowska ◽  
K Rydzyński

Single-strand breaks (SSB) and DNA repair were detected in peripheral lymphocytes derived from workers of a furniture factory in a non-polluted region of Poland. The workers were exposed to wood dust (n = 19), or to the dust and varnishes or lacquers together (n = 5). Four groups were studied simultaneously: (a) exposed workers smokers of cigarettes (n = 14), (b) nonexposed smokers--control (n = 14), (c) exposed workers' nonsmokers (n = 14), (d) exposed nonsmokers (n = 10). In exposed workers DNA SSB and DNA repair were statistically significantly increased. DNA SSB was clearly higher in the smoking workers than in the smoking controls. Cigarette smoking itself has produced no evident increase in the frequency of DNA SSB in the control group. Occupational exposure had a significant effect on DNA repair in non stimulated lymphocytes both in smoking and nonsmoking workers.


Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 58 ◽  
Author(s):  
Lukáš Jakl ◽  
Eva Marková ◽  
Lucia Koláriková ◽  
Igor Belyaev

Purpose: Ionizing radiation induced foci (IRIF) known also as DNA repair foci represent most sensitive endpoint for assessing DNA double strand breaks (DSB). IRIF are usually visualized and enumerated with the aid of fluorescence microscopy using antibodies to γH2AX and 53BP1. This study analyzed effect of low dose ionizing radiation on residual IRIF in human lymphocytes to the aim of potential biodosimetry and possible extrapolation of high-dose γH2AX/53BP1 effects to low doses and compared kinetics of DSB and IRIF. We also analyzed whether DNaseI, which is used for reducing of clumps, affects the IRIF level. Materials and Methods: The cryopreserved human lymphocytes from umbilical cord blood (UCB) were thawed with/without DNaseI, γ-irradiated at doses of 0, 5, 10, and 50 cGy and γH2AX/53BP1 foci were analyzed 30 min, 2 h, and 22 h post-irradiation using appropriate antibodies. We also analyzed kinetics of DSB using PFGE. Results: No significant difference was observed between data obtained by γH2AX foci evaluation in cells that were irradiated by low doses and data obtained by extrapolation from higher doses. Residual 53BP1 foci induced by low doses significantly outreached the data extrapolated from irradiation by higher doses. 53BP1 foci induced by low dose-radiation remain longer at DSB loci than foci induced by higher doses. There was no significant effect of DNaseI on DNA repair foci. Conclusions: Primary γH2AX, 53BP1 foci and their co-localization represent valuable markers for biodosimetry of low doses, but their usefulness is limited by short time window. Residual γH2AX and 53BP1 foci are more useful markers for biodosimetry in vitro. Effects of low doses can be extrapolated from high dose using γH2AX residual foci while γH2AX/53BP1 foci are valuable markers for evaluation of initial DSB induced by ionizing radiation. Residual IRIF induced by low doses persist longer time than those induced by higher doses.


DNA Repair ◽  
2020 ◽  
Vol 89 ◽  
pp. 102828 ◽  
Author(s):  
Aashish Soni ◽  
Tamara Murmann-Konda ◽  
Maria Siemann-Loekes ◽  
Gabriel E. Pantelias ◽  
George Iliakis

2008 ◽  
Vol 65 (8) ◽  
pp. 613-618 ◽  
Author(s):  
Branka Djurovic ◽  
Vesna Spasic-Jokic ◽  
Branislav Djurovic

Background/Aim. During exposure to low-level doses (LLD) of ionizing radiation (IR), the most of harmful effects are produced indirectly, through radiolysis of water and formation of reactive oxygen species (ROS). The antioxidant enzymes - superoxide dismutase (SOD): manganese SOD (MnSOD) and copper-zinc SOD (CuZnSOD), as well as glutathione (GSH), are the most important intracellular antioxidants in the metabolism of ROS. Overproduction of ROS challenges antioxidant enzymes. The aim of this study was to examine if previous exposure to low doses of IR induces adaptive response by means of stimulation of intracellular antioxidant defense system. Methods. We investigated a group of medical workers occupationally exposed to IR (n = 44), 29 male and 15 female. The controls (n = 33) consisted of medical workers not exposed to IR, 23 male and 10 female. The examinees from both groups worked in the same environment and matched in crucial characteristics. All measurements were performed by a calibrated thermoluminiscent dosimeter type CaF2:Mn. SOD activity and GSH content were measured spectrophotometrically in the plasma of both groups of medical workers. Half of each blood sample was irradiated by 2Gy of ? radiation, dose-rate 0.45 Gy/min, and the distance from the source of 74 cm. Results. The dosimetry results indicate that occupational doses were very low. Our results confirmed significantly higher SOD activity in the exposed vs. unexposed workers (p < 0.00006). SOD activity after irradiation of blood samples failed to show a significant difference between the exposed workers and the controls (p = 0.905), even the difference in each group before and after the irradiation was significant. In blood samples of the exposed workers expression of enzymes after the irradiation, was not as high as in the controls, or even in the case of the exposed in nuclear medicine personnel, SOD activity was decreased. There were no significant differences in the content of GSH between the groups. Conclusion. Our results pointed out that occupational exposure to low doses of IR compromised mitochondrial function. During occupational exposure, the activity of antioxidant enzymes was increased as a protection against the increased production of ROS. After high-dose irradiation dysfunction of mitochondrial system was noticed, suggesting the break-down of antioxidant defense and failure of an adaptive response. Therefore, the "chronic oxidative stress" might reduce antioxidant defense in the case of accidental exposure to high doses of IR. It could indirectly increase the incidence of some other "free radicals' diseases" in occupationally exposed personnel. .


2013 ◽  
Vol 52 (3) ◽  
pp. 303-319 ◽  
Author(s):  
Gaël P. Hammer ◽  
Ulrike Scheidemann-Wesp ◽  
Florence Samkange-Zeeb ◽  
Henryk Wicke ◽  
Kazuo Neriishi ◽  
...  

2012 ◽  
Vol 28 (4) ◽  
pp. 1406-1412 ◽  
Author(s):  
JIFANG LIU ◽  
MIN HOU ◽  
TAIZE YUAN ◽  
GAO YI ◽  
SHUXU ZHANG ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document