scholarly journals Enhanced cytotoxic effect of low doses of metformin combined with ionizing radiation on hepatoma cells via ATP deprivation and inhibition of DNA repair

2012 ◽  
Vol 28 (4) ◽  
pp. 1406-1412 ◽  
Author(s):  
JIFANG LIU ◽  
MIN HOU ◽  
TAIZE YUAN ◽  
GAO YI ◽  
SHUXU ZHANG ◽  
...  
Keyword(s):  
Dna Repair ◽  
Ionizing Radiation ◽  
Cytotoxic Effect ◽  
Hepatoma Cells ◽  
Low Doses

scholarly journals Biodosimetry of Low Dose Ionizing Radiation Using DNA Repair Foci in Human Lymphocytes

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 58 ◽  
Author(s):  
Lukáš Jakl ◽  
Eva Marková ◽  
Lucia Koláriková ◽  
Igor Belyaev
Keyword(s):  
Dna Repair ◽  
Ionizing Radiation ◽  
Low Dose ◽  
Time Window ◽  
Human Lymphocytes ◽  
High Dose ◽  
Low Doses ◽  
Significant Difference ◽  
Kinetics Of ◽  
Higher Doses

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.

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 ◽  
...  
Keyword(s):  
Dna Repair ◽  
Occupational Exposure ◽  
Ionizing Radiation ◽  
Linear Regression Analysis ◽  
Detoxification Enzymes ◽  
Low Doses ◽  
Gstt1 Null Genotype ◽  
Genotoxic Damage ◽  
Chromosome Breaks ◽  
Exposed Workers

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.

Radiopharmacology: Hazard or/and Benefit

1984 ◽  
Vol 23 (02) ◽  
pp. 87-91 ◽  
Author(s):  
K. Flemming
Keyword(s):  
Ionizing Radiation ◽  
Late Effects ◽  
Radiation Risk ◽  
Dose Effect ◽  
Radiation Hazard ◽  
Radiation Doses ◽  
Low Doses ◽  
Medical Radiology ◽  
Experimental Findings ◽  
In The Beginning

SummaryIn the beginning of medical radiology, only the benefit of ionizing radiation was obvious, and radiation was handled and applied generously. After late effects had become known, the radiation exposure was reduced to doses following which no such effects were found. Thus, it was assumed that one could obtain an optimal medical benefit without inducing any hazard. Later, due to experimental findings, hypotheses arose (linear dose-effect response, no time factor) which led to the opinion that even low and lowest radiation doses were relevant for the induction of late effects. A radiation fear grew, which was unintentionally strengthened by radiation protection decrees: even for low doses a radiation risk could be calculated. Therefore, it was believed that there could still exist a radiation hazard, and the radiation benefit remained in question. If, however, all presently known facts are considered, one must conclude that large radiation doses are hazardous and low doses are inefficient, whereas lowest doses have a biopositive effect. Ionizing radiation, therefore, may cause both, hazard as well as benefit. Which of the two effects prevails is determined by the level of dose.

Characterization of gene expression profiles at low and very low doses of ionizing radiation

DNA Repair ◽  
2013 ◽  
Vol 12 (7) ◽  
pp. 508-517 ◽  
Author(s):  
Ingrid Nosel ◽  
Aurélie Vaurijoux ◽  
Joan-Francesc Barquinero ◽  
Gaetan Gruel
Keyword(s):  
Gene Expression ◽  
Ionizing Radiation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Low Doses
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