The role of DNA damage in the induction of apoptosis in human lymphocytes by ionizing radiation and radiomimetic agents

1997 ◽  
Vol 75 (4) ◽  
pp. 467
Author(s):  
S P Cregan ◽  
D L Brown ◽  
B P Smith ◽  
REJ Mitchel
1994 ◽  
Vol 72 (11-12) ◽  
pp. 475-482 ◽  
Author(s):  
S. P. Cregan ◽  
D. R. Boreham ◽  
P. R. Walker ◽  
D. L. Brown ◽  
R. E. J. Mitchel

We have investigated the influence of the cellular adaptive response to ionizing radiation on radiation-induced apoptosis in human cells. The adaptive response is believed to be a protective mechanism that confers resistance to the detrimental effects of ionizing radiation and that can be induced by different agents, including hyperthermia and radiation. We have used fluorescence analysis of DNA unwinding (FADU) to assay the induction of apoptosis in human peripheral blood lymphocytes by ionizing radiation. Using the FADU assay, we have observed the initial radiation-induced DNA damage, its subsequent disappearance due to enzymatic repair, and its time- and dose-dependent reappearance. We believe this reappearance of DNA damage to be indicative of the DNA fragmentation event associated with apoptosis. This interpretation has been supported at the individual cell level using an in situ terminal deoxynucleotidyl transferase (TDT) assay (Apoptag, Oncor Inc.), which detects the 3′-hydroxyl ends of fragmented DNA, and by fluorescence analysis of nuclear morphology in Hoechst 33258 stained cells. Pretreatment of cells with low-dose γ-radiation (0.1 Gy) or mild hyperthermia (40 °C for 30 min) altered the extent of radiation-induced (3 Gy) apoptosis. Both pretreatments sensitized lymphocytes to become apoptotic after the 3-Gy radiation exposure. This sensitization may represent an adaptive response mechanism that reduces the risk that genetically damaged cells will proliferate. The ability to modify the probability of radiation-induced apoptosis may lower the cancer risk from a radiation exposure.Key words: apoptosis, adaptive response, ionizing radiation, hyperthermia.


1992 ◽  
Vol 43 (4) ◽  
pp. 705-715 ◽  
Author(s):  
Birgit Peter ◽  
Marjolein Wartena ◽  
Harm H. Kampinga ◽  
Antonius W.T. Konings

Author(s):  
Emiliano Basso ◽  
Giulia Regazzo ◽  
Mario Fiore ◽  
Valentina Palma ◽  
Gianandrea Traversi ◽  
...  

2021 ◽  
Vol 000 (000) ◽  
pp. 000-000
Author(s):  
Chengyou Jia ◽  
Qiang Wang ◽  
Xinhuang Yao ◽  
Jianshe Yang

1998 ◽  
Vol 45 (3) ◽  
pp. 701-704 ◽  
Author(s):  
M Kruszewski ◽  
T Iwaneńko

The role of nuclear proteins in protection of DNA against ionizing radiation and their contribution to the radiation sensitivity was examined by an alkaline version of comet assay in two L5178Y (LY) mouse lymphoma cell lines differing in sensitivity to ionizing radiation. LY-S cells are twice more sensitive to ionizing radiation than LY-R cells (D0 values of survival curves are 0.5 Gy and 1 Gy, respectively). Sequential removal of nuclear proteins by extraction with NaCl of different concentrations increased the X-ray induced DNA damage in LY-R nucleoids. In contrast, in the radiation sensitive LY-S cell line, depletion of nuclear proteins practically did not affect DNA damage. Although there is no doubt that the main cause of LYS cells' sensitivity to ionizing radiation is a defect in the repair of double-strand breaks, our data support the concept that nuclear matrix organisation may contribute to the cellular susceptibility to DNA damaging agents.


Author(s):  
Sherien Montaser ◽  
Gehan Roshdy Abdel Hamid ◽  
Ahmad Rashad Aboghadeer

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247776
Author(s):  
Ahmad Salimi ◽  
Elahe Baghal ◽  
Hassan Ghobadi ◽  
Niloufar Hashemidanesh ◽  
Farzad Khodaparast ◽  
...  

Acrylamide (AA), is an important contaminant formed during food processing under high temperature. Due to its potential neurotoxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, genotoxicity and carcinogenicity effects, this food contaminant has been recognized as a human health concern. Previous studies showed that acrylamide-induced toxicity is associated with active metabolite of acrylamide by cytochrome P450 enzyme, oxidative stress, mitochondrial dysfunction and DNA damage. In the current study, we investigated the role of oxidative stress in acrylamide’s genotoxicity and therapeutic potential role of ellagic acid (EA) in human lymphocytes. Human lymphocytes were simultaneously treated with different concentrations of EA (10, 25 and 50 μM) and acrylamide (50 μM) for 4 h at 37°C. After 4 hours of incubation, the toxicity parameters such cytotoxicity, ROS formation, oxidized/reduced glutathione (GSH/GSSG) content, malondialdehyde (MDA) level, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse and 8-hydroxy-2’-deoxyguanosine (8-OHdG) were analyzed using biochemical and flow cytometry evaluations. It has been found that acrylamide (50 μM) significantly increased cytotoxicity, ROS formation, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage in human lymphocytes. On the other hand, cotreatment with EA (25 and 50 μM) inhibited AA-induced oxidative stress which subsequently led to decreasing of the cytotoxicity, GSH oxidation, lipid peroxidation, MMP collapse, lysosomal and DNA damage. Together, these results suggest that probably the co-exposure of EA with foods containing acrylamide could decrease mitochondrial, lysosomal and DNA damages, and oxidative stress induced by acrylamide in human body.


2001 ◽  
Vol 37 ◽  
pp. S278
Author(s):  
C. Gruber ◽  
J. Wagner ◽  
P. Marini ◽  
J. Rudner ◽  
K. Schulze-Osthoff ◽  
...  

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