Comparison of biological effects of DNA damage induced by ionizing radiation and hydrogen peroxide in CHO cells

ABSTRACT The bacterium Deinococcus radiodurans is resistant to extremely high levels of DNA-damaging agents such as UV light, ionizing radiation, and chemicals such as hydrogen peroxide and mitomycin C. The organism is able to repair large numbers of double-strand breaks caused by ionizing radiation, in spite of the lack of the RecBCD enzyme, which is essential for double-strand DNA break repair in Escherichia coli and many other bacteria. The D. radiodurans genome sequence indicates that the organism lacks recB and recC genes, but there is a gene encoding a protein with significant similarity to the RecD protein of E. coli and other bacteria. We have generated D. radiodurans strains with a disruption or deletion of the recD gene. The recD mutants are more sensitive than wild-type cells to irradiation with gamma rays and UV light and to treatment with hydrogen peroxide, but they are not sensitive to treatment with mitomycin C and methyl methanesulfonate. The recD mutants also show greater efficiency of transformation by exogenous homologous DNA. These results are the first indication that the D. radiodurans RecD protein has a role in DNA damage repair and/or homologous recombination in the organism.

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Role of DNA Damage and Repair in Detrimental Effects of Ionizing Radiation

Radiation ◽

10.3390/radiation1010001 ◽

2020 ◽

Vol 1 (1) ◽

pp. 1-4

Author(s):

Alexandros G. Georgakilas

Keyword(s):

Dna Damage ◽

Ionizing Radiation ◽

Biological Effects ◽

Full Range ◽

High Quality Research ◽

Dna Damage And Repair ◽

Biological Damage ◽

Biological Responses ◽

Technical Advances ◽

Living Organisms

Ionizing radiation (IR) is considered a traditional mutagen and genotoxic agent. Exposure to IR affects in all cases biological systems and living organisms from plants to humans mostly in a pernicious way. At low (<0.1 Gy) and low-to-medium doses (0.1–1 Gy), one can find in the literature a variety of findings indicating sometimes a positive-like anti-inflammatory effect or detrimental-like toxicity. In this Special Issue and in general in the current research, we would like to acquire works and more knowledge on the role(s) of DNA damage and its repair induced by ionizing radiations as instigators of the full range of biological responses to radiation. Emphasis should be given to advances offering mechanistic insights into the ability of radiations with different qualities to severely impact cells or tissues. High-quality research or review studies on different species projected to humans are welcome. Technical advances reporting on the methodologies to accurately measure DNA or other types of biological damage must be highly considered for the near future in our research community, as well. Last but not least, clinical trials or protocols with improvements to radiation therapy and radiation protection are also included in our vision for the advancement of research regarding biological effects of IR.

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Hydrogen peroxide induced by modulated electromagnetic radiation protects the cells from DNA damage

Open Life Sciences ◽

10.2478/s11535-014-0326-x ◽

2014 ◽

Vol 9 (10) ◽

pp. 915-921 ◽

Cited By ~ 2

Author(s):

Andrew Gapeyev ◽

Nina Lukyanova ◽

Sergey Gudkov

Keyword(s):

Hydrogen Peroxide ◽

Dna Damage ◽

Ionizing Radiation ◽

Electromagnetic Radiation ◽

Modulation Frequency ◽

Preliminary Treatment ◽

X Rays ◽

Blood Leukocytes ◽

Nonspecific Resistance ◽

Low Level

AbstractIt is believed that non-ionizing electromagnetic radiation (EMR) and low-level hydrogen peroxide (H2O2) may change nonspecific resistance and modify DNA damage caused by ionizing radiation. To check this assumption, the combined effects of extremely high-frequency EMR (EHF EMR) and X-rays on induction of DNA damage in mouse whole blood leukocytes were studied. The cells were exposed to X-rays with or without preliminary treatment with EHF EMR or low-level H2O2. With the use of enhanced chemiluminescence, it was shown for the first time that pulse-modulated EHF EMR (42.2 GHz, incident power density of 0.1 mW/cm2, exposure duration of 20 min, modulation frequency of 1 Hz) induced H2O2 at a concentration of 4.6 ± 0.3 nM L−1 in physiological saline. With the use of an alkaline comet assay, it was found that the exposure of cells to the pulse-modulated EHF EMR, 25 min prior to treatment with X-rays at a dose of 4 Gy reduced the level of ionizing radiation-induced DNA damage. Continuous EHF EMR was inefficient. In turn, it was shown that low-level H2O2 (30–500 nM L−1) protected the cells against X-irradiation. Thus, the mechanisms of radiation protective effect of EHF EMR are connected with the induction of the adaptive response by nanomolar concentrations of reactive oxygen species formed by pulse-modulated EHF EMR.

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

Mutagenesis ◽

10.1093/mutage/18.2.119 ◽

2003 ◽

Vol 18 (2) ◽

pp. 119-126 ◽

Cited By ~ 28

Author(s):

W. Greenrod ◽

M. Fenech

Keyword(s):

Hydrogen Peroxide ◽

Dna Damage ◽

Ionizing Radiation ◽

Human Lymphocytes ◽

Radiation Induced

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Catalase T-Deficient Fission Yeast Meiocytes Show Resistance to Ionizing Radiation

Antioxidants ◽

10.3390/antiox9090881 ◽

2020 ◽

Vol 9 (9) ◽

pp. 881 ◽

Cited By ~ 1

Author(s):

Razan Muhtadi ◽

Alexander Lorenz ◽

Samantha J. Mpaulo ◽

Christian Siebenwirth ◽

Harry Scherthan

Keyword(s):

Hydrogen Peroxide ◽

Dna Damage ◽

Ionizing Radiation ◽

Fission Yeast ◽

Defense Mechanisms ◽

Meiotic Chromosome ◽

Premature Aging ◽

Wild Type ◽

Moderate Sensitivity

Environmental stress, reactive oxygen species (ROS), or ionizing radiation (IR) can induce adverse effects in organisms and their cells, including mutations and premature aging. DNA damage and its faulty repair can lead to cell death or promote cancer through the accumulation of mutations. Misrepair in germ cells is particularly dangerous as it may lead to alterations in developmental programs and genetic disease in the offspring. DNA damage pathways and radical defense mechanisms mediate resistance to genotoxic stresses. Here, we investigated, in the fission yeast Schizosaccharomyces pombe, the role of the H2O2-detoxifying enzyme cytosolic catalase T (Ctt1) and the Fe2+/Mn2+ symporter Pcl1 in protecting meiotic chromosome dynamics and gamete formation from radicals generated by ROS and IR. We found that wild-type and pcl1-deficient cells respond similarly to X ray doses of up to 300 Gy, while ctt1∆ meiocytes showed a moderate sensitivity to IR but a hypersensitivity to hydrogen peroxide with cells dying at >0.4 mM H2O2. Meiocytes deficient for pcl1, on the other hand, showed a resistance to hydrogen peroxide similar to that of the wild type, surviving doses >40 mM. In all, it appears that in the absence of the main H2O2-detoxifying pathway S. pombe meiocytes are able to survive significant doses of IR-induced radicals.

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Cells Lacking the PolQ Polymerase Are Moderately Sensitive to Ionizing Radiation and the Oxidant Induced Toxicity of Paraquat and Bleomycin.

Blood ◽

10.1182/blood.v110.11.4037.4037 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4037-4037

Author(s):

Julie P. Goff ◽

Michael W. Epperly ◽

Donna S. Shields ◽

Tracy Smith ◽

Mineaki Seki ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Dna Damage ◽

Ionizing Radiation ◽

Peripheral Blood ◽

Excision Repair ◽

Dna Breaks ◽

Thymine Glycol ◽

Abasic Sites ◽

Significant Difference ◽

Base Excision

Abstract The DNA polymerase POLQ (pol theta) can bypass abasic sites in DNA and thymine glycol, a common product of reactive oxygen species damage to DNA. POLQ may also have a back-up role in base excision repair. To explore the role of POLQ in tolerance of DNA damage following irradiation, and exposure to agents that induce oxidative stress we established bone marrow stromal cell lines from the PolQ+/+ and PolQ−/− mice. Irradiation survival curves were obtained for PolQ +/+, and 2 clones of PolQ −/− cells. Dose-response experiments using the free radical generators paraquat, hydrogen peroxide and bleomycin were done on 2 clones each of PolQ +/+ and PolQ −/− cells. There was no significant difference over 23 weeks in cumulative granulopoiesis in LTBMCs from PolQ +/+ and PolQ −/− mice. PolQ+/+ cells and 2 independent clones of PolQ−/− cells were exposed to 0 – 8 Gy of gamma radiation, and colony forming ability was measured. PolQ −/− cells were more sensitive to irradiation as shown by decreased Do from 1.38 + 0.06 Gy for PolQ +/+ cells compared to 1.27 + 0.16 and 0.98 + 0.10 (p = 0.0316) Gy for PolQ −/− clones 1 and 3 respectively. Micronucleated reticulocytes were measured in peripheral blood of PolQ+/+, +/− or −/− mice after irradiation with 75 cGy or 700 cGy. Before irradiation, PolQ−/− mice had a higher fraction of MN- reticulocytes compared to PolQ+/+. Forty hr after irradiation, MN reticulocytes in PolQ−/− mice increased to 8.53 ± 1.48%, compared to 2.35 ± 0.12% and 2.55 ± 0.17% in PolQ+/+ mice (p = 0.0032). PolQ +/+ and PolQ −/− cells were exposed to paraquat (0–20 mM), hydrogen peroxide (0–40 uM) and bleomycin (0–5 ug/ml) for 1 hr prior to plating. After 7 days, the cells were stained and colonies of 50 cells or greater were counted. Statistical analysis was done using ANCOVA. PolQ −/− cells were modestly more sensitive to paraquat (p< 0.0001) and bleomycin (p< 0.0001) than PolQ +/+ cells. When the cells were treated with hydrogen peroxide, there was no significant difference in surviving fraction (p=0.7327) between the PolQ +/+ and the −/− cells. The moderate but significant sensitivity of POLQ-defective cells to bleomycin, ionizing radiation and paraquat supports the hypothesis that POLQ normally participates in helping cells tolerate DNA damage. The increased frequencies of spontaneous and radiation-induced micronuclei in peripheral blood red cells indicate that POLQ has a role in maintaining genomic integrity via limiting double-strand DNA breaks.

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