Radiation-Induced DNA Damage in Tumors and Normal Tissues. III. Oxygen Dependence of the Formation of Strand Breaks and DNA-Protein Crosslinks

1995 ◽  
Vol 142 (2) ◽  
pp. 163 ◽  
Author(s):  
H. Zhang ◽  
C. J. Koch ◽  
C. A. Wallen ◽  
K. T. Wheeler
Keyword(s):  
Dna Damage ◽  
Strand Breaks ◽  
Normal Tissues ◽  
Radiation Induced ◽  
Protein Crosslinks

KGF facilitates repair of radiation-induced DNA damage in alveolar epithelial cells

1997 ◽  
Vol 272 (6) ◽  
pp. L1174-L1180 ◽  
Author(s):  
M. Takeoka ◽  
W. F. Ward ◽  
H. Pollack ◽  
D. W. Kamp ◽  
R. J. Panos
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Epithelial Cells ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Alveolar Epithelial ◽  
Radiation Induced ◽  
Dna Strand

Administration of exogenous keratinocyte growth factor (KGF) prevents or attenuates several forms of oxidant-mediated lung injury. Because DNA damage in epithelial cells is a component of radiation pneumotoxicity, we determined whether KGF ameliorated DNA strand breaks in irradiated A549 cells. Cells were exposed to 137Cs gamma rays, and DNA damage was measured by alkaline unwinding and ethidium bromide fluorescence after a 30-min recovery period. Radiation induced a dose-dependent increase in DNA strand breaks. The percentage of double-stranded DNA after exposure to 30 Gy increased from 44.6 +/- 3.5% in untreated control cells to 61.6 +/- 5.0% in cells cultured with 100 ng/ml KGF for 24 h (P < 0.05). No reduction in DNA damage occurred when the cells were cultured with KGF but maintained at 0 degree C during and after irradiation. The sparing effect of KGF on radiation-induced DNA damage was blocked by aphidicolin, an inhibitor of DNA polymerases-alpha, -delta, and -epsilon and by butylphenyl dGTP, which blocks DNA polymerase-alpha strongly and polymerases-delta and -epsilon less effectively. However, dideoxythymidine triphosphate, a specific inhibitor of DNA polymerase-beta, did not abrogate the KGF effect. Thus KGF increases DNA repair capacity in irradiated pulmonary epithelial cells, an effect mediated at least in part by DNA polymerases-alpha, -delta, and -epsilon. Enhancement of DNA repair capability after cell damage may be one mechanism by which KGF is able to ameliorate oxidant-mediated alveolar epithelial injury.

scholarly journals Protective Activity of C-Geranylflavonoid Analogs from Paulownia tomentosa against DNA Damage in 137Cs Irradiated AHH-1Cells

2014 ◽  
Vol 9 (9) ◽  
pp. 1934578X1400900
Author(s):  
Hyung-In Moon ◽  
Min Ho Jeong ◽  
Wol Soon Jo
Keyword(s):  
Dna Damage ◽  
Protective Effects ◽  
Strand Breaks ◽  
Human Lymphoblastoid Cell ◽  
Wide Range ◽  
Radiation Induced ◽  
Anti Oxidant ◽  
Dna Strand ◽  
Cellular Dna

Radiotherapy is an important form of treatment for a wide range of cancers, but it can damage DNA and cause adverse effects. We investigated if the diplacone analogs of P. tomentosa were radio-protective in a human lymphoblastoid cell line (AHH-1). Four geranylated flavonoids, diplacone, 3′- O-methyl-5′-hydroxydiplacone, 3′- O-methyl-5′- O-methyldiplacone and 3′- O-methyldiplacol, were tested for their antioxidant and radio-protective effects. Diplacone analogs effectively scavenged free radicals and inhibited radiation-induced DNA strand breaks in vitro. They significantly decreased levels of reactive oxygen species and cellular DNA damage in 2 Gy-irradiated AHH-1 cells. Glutathione levels and superoxide dismutase activity in irradiated AHH-1 cells increased significantly after treatment with these analogs. The enhanced biological anti-oxidant activity and radioprotective activity of diplacone analogs maintained the survival of irradiated AHH-1 cells in a clonogenic assay. These data suggest that diplacone analogs may protect healthy tissue surrounding tumor cells during radiotherapy to ensure better control of radiotherapy and allow higher doses of radiotherapy to be employed.

scholarly journals Influence of Acute Exercise on DNA Repair and PARP Activity before and after Irradiation in Lymphocytes from Trained and Untrained Individuals

2019 ◽  
Vol 20 (12) ◽  
pp. 2999 ◽  
Author(s):  
Maria Moreno-Villanueva ◽  
Andreas Kramer ◽  
Tabea Hammes ◽  
Maria Venegas-Carro ◽  
Patrick Thumm ◽  
...  
Keyword(s):  
Physical Activity ◽  
Dna Damage ◽  
Dna Repair ◽  
Immune Cells ◽  
Acute Exercise ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Before And After ◽  
Radiation Induced ◽  
Dna Strand

Several studies indicate that acute exercise induces DNA damage, whereas regular exercise increases DNA repair kinetics. Although the molecular mechanisms are not completely understood, the induction of endogenous reactive oxygen species (ROS) during acute exhaustive exercise due to metabolic processes might be responsible for the observed DNA damage, while an adaptive increase in antioxidant capacity due to regular physical activity seems to play an important protective role. However, the protective effect of physical activity on exogenously induced DNA damage in human immune cells has been poorly investigated. We asked the question whether individuals with a high aerobic capacity would have an enhanced response to radiation-induced DNA damage. Immune cells are highly sensitive to radiation and exercise affects lymphocyte dynamics and immune function. Therefore, we measured endogenous and radiation-induced DNA strand breaks and poly (ADP-ribose) polymerase-1 (PARP1) activity in peripheral blood mononuclear cells (PBMCs) from endurance-trained (maximum rate of oxygen consumption measured during incremental exercise V’O2max > 55 mL/min/kg) and untrained (V’O2max < 45 mL/min/kg) young healthy male volunteers before and after exhaustive exercise. Our results indicate that: (i) acute exercise induces DNA strand breaks in lymphocytes only in untrained individuals, (ii) following acute exercise, trained individuals repaired radiation-induced DNA strand breaks faster than untrained individuals, and (iii) trained subjects retained a higher level of radiation-induced PARP1 activity after acute exercise. The results of the present study indicate that increased aerobic fitness can protect immune cells against radiation-induced DNA strand breaks.

scholarly journals H2A.X Phosphorylation in Oxidative Stress and Risk Assessment in Plasma Medicine

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Clarissa S. Schütz ◽  
Matthias B. Stope ◽  
Sander Bekeschus
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Double Strand Breaks ◽  
Plasma Medicine ◽  
Mutagenic Potential ◽  
Strand Breaks ◽  
Radiation Induced ◽  
And Function ◽  
Physical Plasma ◽  
Suitable Marker

At serine139-phosphorylated gamma histone H2A.X (γH2A.X) has been established over the decades as sensitive evidence of radiation-induced DNA damage, especially DNA double-strand breaks (DSBs) in radiation biology. Therefore, γH2A.X has been considered a suitable marker for biomedical applications and a general indicator of direct DNA damage with other therapeutic agents, such as cold physical plasma. Medical plasma technology generates a partially ionized gas releasing a plethora of reactive oxygen and nitrogen species (ROS) simultaneously that have been used for therapeutic purposes such as wound healing and cancer treatment. The quantification of γH2A.X as a surrogate parameter of direct DNA damage has often been used to assess genotoxicity in plasma-treated cells, whereas no sustainable mutagenic potential of the medical plasma treatment could be identified despite H2A.X phosphorylation. However, phosphorylated H2A.X occurs during apoptosis, which is associated with exposure to cold plasma and ROS. This review summarizes the current understanding of γH2A.X induction and function in oxidative stress in general and plasma medicine in particular. Due to the progress towards understanding the mechanisms of H2A.X phosphorylation in the absence of DSB and ROS, observations of γH2A.X in medical fields should be carefully interpreted.

DNA Methyltransferases Modulate the Bystander Effect in Mouse Embryonic Stem Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4154-4154
Author(s):  
Rebecca E. Rugo ◽  
Michael W. Epperly ◽  
Darcy Franicola ◽  
Benjamin Greenberger ◽  
Paavani Komanduri ◽  
...  
Keyword(s):  
Dna Damage ◽  
Bystander Effect ◽  
Embryonic Stem ◽  
Dna Methyltransferases ◽  
Epigenetic Mechanisms ◽  
Bystander Effects ◽  
Strand Breaks ◽  
Radiation Induced ◽  
Bystander Cells ◽  
Gpx Activity

Abstract Cells exposed to radiation or other genotoxic agents can induce DNA damage and other stress responses in non-irradiated cells that are either cultured with the irradiated cells or have been exposed to culture medium from irradiated cells. This is called the bystander effect. In a previous study we found that the descendents of bystander cells exposed to Mitomycin C (MMC) are themselves capable of inducing homologous recombination in un-exposed cells. This suggests that MMC induces persistent and transmissible changes in expression in bystander cells. Bystander effects are likely caused by epigenetic mechanisms rather than “classic” mutations, i.e. changes in DNA sequence. One of the epigenetic mechanisms cells employ for changing expression is DNA methylation in which DNA methyltransferases (DNMTs) add a methyl group to the 5 carbon of cytosine. In this study we asked if ionizing radiation can induce transmissible DNA damage in bystander cells by examining if bystander cells exposed to irradiated cells were themselves able to induce damage in naive cells. Furthermore, we asked if this was dependent on DNMT activity in the irradiated cells. We irradiated wild-type (WT) and DNMT triple knockout (DNMT TKO) mouse embryonic stem cells (ESCs) and after two weeks of continuous culture, we collected conditioned medium (CM). CM was then added to cultures of naive WT ESCs (primary bystanders). Three weeks later, CM was collected from the primary bystanders and added to naïve WT cells (secondary bystanders). We assessed DNA damage by evaluating strand breaks using the alkaline Comet assay and sister chromatid exchange (SCE) analysis. As expected, we found that medium from cells irradiated with 5 Gy induced modest damage in bystander cells. The median Olive tail moment was 2.8 in bystander cells exposed to conditioned medium from irradiated cells compared to 1.0 in control bystander cells (p < 0.0001). Homologous recombination was 0.15 chromatid exchanges per chromosome compared to 0.092 in control bystanders (p < 0.0001). We also observed an increase in strand breaks in secondary bystanders of a similar magnitude to that found in primary bystanders, indicating that radiation-induced bystanders are themselves able to induce damage. In contrast to WT cells, the irradiated DNMT TKO cells did not induce strand breaks in bystander cells, as measured by the Comet assay, but did induce HR. Surprisingly, we also observed that un-irradiated DNMT TKO cells induce DNA damage in bystanders, and furthermore that the magnitude of the effect is similar to that induced by irradiated WT cells. These data suggest that methyltransferases have a complex role in bystander effects. Bystander effects may be mediated by free radicals. To see if the DNMT TKO cells had changes in antioxidant levels, glutathione (GSH) and glutathione peroxidase (GPX) activity were determined. There was no significant change in GSH levels between WT and DNMT TKO cells. However, DNMT TKO cells had significantly higher levels of GPX activity (275.4 + 19.8 mU/mg protein) compared to control cells (122.0 + 16.4 mU/mg, p= 0.0001). Taken together, these results show that radiation-induced bystander cells can themselves induce damage in un-irradiated cells and suggest that cells lacking DNA methylation activity can induce bystander effects.

scholarly journals The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair

2005 ◽  
Vol 25 (5) ◽  
pp. 1949-1957 ◽  
Author(s):  
Huimei Lu ◽  
Xu Guo ◽  
Xiangbing Meng ◽  
Jingmei Liu ◽  
Chris Allen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genome Stability ◽  
Recombinational Repair ◽  
Dna Double Strand Breaks ◽  
Focus Formation ◽  
Interacting Protein ◽  
Strand Breaks ◽  
Homologous Recombinational Repair ◽  
Radiation Induced ◽  
Nuclear Foci

ABSTRACT Homologous recombinational repair (HRR) of DNA damage is critical for maintaining genome stability and tumor suppression. RAD51 and BRCA2 colocalization in nuclear foci is a hallmark of HRR. BRCA2 has important roles in RAD51 focus formation and HRR of DNA double-strand breaks (DSBs). We previously reported that BCCIPα interacts with BRCA2. We show that a second isoform, BCCIPβ, also interacts with BRCA2 and that this interaction occurs in a region shared by BCCIPα and BCCIPβ. We further show that chromatin-bound BRCA2 colocalizes with BCCIP nuclear foci and that most radiation-induced RAD51 foci colocalize with BCCIP. Reducing BCCIPα by 90% or BCCIPβ by 50% by RNA interference markedly reduces RAD51 and BRCA2 foci and reduces HRR of DSBs by 20- to 100-fold. Similarly, reducing BRCA2 by 50% reduces RAD51 and BCCIP foci. These data indicate that BCCIP is critical for BRCA2- and RAD51-dependent responses to DNA damage and HRR.

Early stage of nucleic acid electrochemistry. Detection of DNA damage in X-ray-irradiated rats

2011 ◽  
Vol 76 (12) ◽  
pp. 1799-1810 ◽  
Author(s):  
Emil Paleček
Keyword(s):  
Dna Damage ◽  
Nucleic Acid ◽  
Dna Analysis ◽  
Early Stage ◽  
High Sensitivity ◽  
Strand Breaks ◽  
X Ray ◽  
Dna And Rna ◽  
Oscillographic Polarography ◽  
Radiation Induced

First papers on electroactivity of DNA and RNA were published more then 50 years ago. For about 8 years oscillographic polarography at controlled a.c. (OP, proposed by J. Heyrovský already in 1941) was the method of choice for DNA analysis. Since approximately 1954 Robert Kalvoda developed OP for wide application in various fields. It is shown that already before 1960 it was possible to detect damage to DNA in X-ray-irradiated rats by means of OP. DNA samples from irradiated animals produced significantly larger OP anodic guanine signal indicating changes in the DNA structure. At present, radiation-induced strand breaks and damage to bases in DNA can be electrochemically detected at high sensitivity.

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