scholarly journals The principal phenolic and alcoholic components of wine protect human lymphocytes against hydrogen peroxide- and ionizing radiation-induced DNA damage in vitro

Mutagenesis ◽  
2003 ◽  
Vol 18 (2) ◽  
pp. 119-126 ◽  
Author(s):  
W. Greenrod ◽  
M. Fenech
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Human Lymphocytes ◽  
Radiation Induced

Modification of radiation-induced apoptosis in radiation- or hyperthermia-adapted human lymphocytes

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
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Adaptive Response ◽  
Human Peripheral Blood ◽  
Human Lymphocytes ◽  
Fluorescence Analysis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Protective Mechanism ◽  
Radiation Induced ◽  
Induced Apoptosis

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.

Resveratrol affects DNA damage induced by ionizing radiation in human lymphocytes in vitro

2016 ◽  
Vol 806 ◽  
pp. 40-46 ◽  
Author(s):  
Emiliano Basso ◽  
Giulia Regazzo ◽  
Mario Fiore ◽  
Valentina Palma ◽  
Gianandrea Traversi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Human Lymphocytes

Protection and Mitigation by Resveratrol of DNA Damage Induced in Irradiated Human Lymphocytes In Vitro

2021 ◽  
Author(s):  
Małgorzata M. Dobrzyńska ◽  
Aneta Gajowik
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Radiation Exposure ◽  
Human Lymphocytes ◽  
Radiation Induced ◽  
Dose Dependent

The aim of this study was to examine the protective and/or mitigative properties of resveratrol (RSV) administered before or after irradiation of human lymphocytes in vitro. The isolated lymphocytes were incubated for 1 h with resveratrol, at doses of 0.1 (lowest), 0.5 (medium) or 1 (highest) mM/ml: 1 h before; immediately before; immediately after irradiation; and 1 h after irradiation with 0.5, 1 and 2 Gy. The degree of DNA damage was evaluated by Comet Assay. Treatment of human lymphocytes with resveratrol 1 h before or immediately after radiation exposure showed protection from radiation-induced DNA damage. However, 1 Gy irradiation + 1 mM/ml RSV, and 2 Gy irradiation + 0.5 and 1 mM/ml RSV 1 h before irradiation did not provide the same protection. Significant dose-dependent reduction of the level of DNA damage was observed after application of RSV immediately postirradiation or 1 h postirradiation. The reduction in DNA damage was the highest at the 0.1 dose of resveratrol. Our results lead to the conclusion that resveratrol may act both as a radioprotector as well as a radiomitigator. Resveratrol at the lowest (0.5 mM/ml) dose was more effective when combined with 0.5 and 1 Gy doses of radiation.

scholarly journals Truncated PPM1D Prevents Apoptosis in the Murine Thymus and Promotes Ionizing Radiation-Induced Lymphoma

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2068
Author(s):  
Andra S. Martinikova ◽  
Monika Burocziova ◽  
Miroslav Stoyanov ◽  
Libor Macurek
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Tumor Formation ◽  
Cell Cycle Checkpoints ◽  
Negative Regulator ◽  
Tumor Suppressor P53 ◽  
Mouse Thymus ◽  
Truncating Mutation ◽  
T Cell Lymphomas ◽  
Radiation Induced

Genome integrity is protected by the cell-cycle checkpoints that prevent cell proliferation in the presence of DNA damage and allow time for DNA repair. The transient checkpoint arrest together with cellular senescence represent an intrinsic barrier to tumorigenesis. Tumor suppressor p53 is an integral part of the checkpoints and its inactivating mutations promote cancer growth. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of p53. Although its loss impairs recovery from the G2 checkpoint and promotes induction of senescence, amplification of the PPM1D locus or gain-of-function truncating mutations of PPM1D occur in various cancers. Here we used a transgenic mouse model carrying a truncating mutation in exon 6 of PPM1D (Ppm1dT). As with human cell lines, we found that the truncated PPM1D was present at high levels in the mouse thymus. Truncated PPM1D did not affect differentiation of T-cells in the thymus but it impaired their response to ionizing radiation (IR). Thymocytes in Ppm1dT/+ mice did not arrest in the checkpoint and continued to proliferate despite the presence of DNA damage. In addition, we observed a decreased level of apoptosis in the thymi of Ppm1dT/+ mice. Moreover, the frequency of the IR-induced T-cell lymphomas increased in Ppm1dT/+Trp53+/− mice resulting in decreased survival. We conclude that truncated PPM1D partially suppresses the p53 pathway in the mouse thymus and potentiates tumor formation under the condition of a partial loss of p53 function.

scholarly journals A comparison of the in vitro genotoxicity of anticancer drugs idarubicin and mitoxantrone.

2002 ◽  
Vol 49 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Janusz Błasiak ◽  
Ewa Gloc ◽  
Mariusz Warszawski
Keyword(s):  
Dna Damage ◽  
Human Lymphocytes ◽  
Dna Glycosylase ◽  
Oxygen Species ◽  
Anthracycline Antibiotic ◽  
Strand Breaks ◽  
Endonuclease Iii ◽  
Normal Human ◽  
In Vitro Genotoxicity

Idarubicin is an anthracycline antibiotic used in cancer therapy. Mitoxantrone is an anthracycline analog with presumed better antineoplastic activity and lesser toxicity. Using the alkaline comet assaywe showed that the drugs at 0.01-10 microM induced DNA damage in normal human lymphocytes. The effect induced by idarubicin was more pronounced than by mitoxantrone (P < 0.001). The cells treated with mitoxantrone at 1 microM were able to repair damage to their DNA within a 30-min incubation, whereas the lymphocytes exposed to idarubicin needed 180 min. Since anthracyclines are known to produce free radicals, we checked whether reactive oxygen species might be involved in the observed DNA damage. Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by idarubicin, but did not affect the extent evoked by mitoxantrone. Lymphocytes exposed to the drugs and treated with endonuclease III or formamidopyrimidine-DNA glycosylase (Fpg), enzymes recognizing and nicking oxidized bases, displayed a higher level of DNA damage than the untreated ones. 3-Methyladenine-DNA glycosylase II (AlkA), an enzyme recognizing and nicking mainly methylated bases in DNA, increased the extent of DNA damage caused by idarubicin, but not that induced by mitoxantrone. Our results indicate that the induction of secondary malignancies should be taken into account as side effects of the two drugs. Direct strand breaks, oxidation and methylation of the DNA bases can underlie the DNA-damaging effect of idarubicin, whereas mitoxantrone can induce strand breaks and modification of the bases, including oxidation. The observed in normal lymphocytes much lesser genotoxicity of mitoxantrone compared to idarubicin should be taken into account in planning chemotherapeutic strategies.

Irreversible electron attachment – a key to DNA damage by solvated electrons in aqueous solution

2015 ◽  
Vol 13 (41) ◽  
pp. 10362-10369 ◽  
Author(s):  
K. Westphal ◽  
J. Wiczk ◽  
J. Miloch ◽  
G. Kciuk ◽  
K. Bobrowski ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Electron Attachment ◽  
Solvated Electrons ◽  
Radiation Induced

In an aqueous solution trinucleotides labeled with bromonucleobases are damaged by ionizing radiation induced electrons while native trimers are insensitive to electrons under the same conditions.

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