Inducible Repair of Thymine Glycol Detected by an Ultrasensitive Assay for DNA Damage

Science ◽  
1998 ◽  
Vol 280 (5366) ◽  
pp. 1066-1069 ◽  
Author(s):  
X. C. Le
Keyword(s):  
Dna Damage ◽  
Thymine Glycol ◽  
Ultrasensitive Assay ◽  
Inducible Repair

scholarly journals Cellular response to DNA damage is enhanced by the pR plasmid in mouse cells and in Escherichia coli.

1986 ◽  
Vol 6 (2) ◽  
pp. 586-592 ◽  
Author(s):  
L Marcucci ◽  
F Gigliani ◽  
P A Battaglia ◽  
R Bosi ◽  
E Sporeno ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Statistical Analysis ◽  
Cellular Response ◽  
Regulatory Mechanism ◽  
Uv Light ◽  
Transformed Cells ◽  
Insertion Mutagenesis ◽  
Mouse Cells ◽  
Inducible Repair

The pR plasmid, which enhances the survival of Escherichia coli C600 exposed to UV light by induction of the SOS regulatory mechanism, showed the same effect when it transformed mouse LTA cells (tk-, aprt-). With Tn5 insertion mutagenesis which inactivates UV functions in the pR plasmid, we recognized two different regions of the plasmid, uvp1 and uvp2. These pR UVR- mutants exhibited the same effect in LTA transformed cells, demonstrating that resistance to UV light, carried by the pR plasmid, was really due to the expression of these two regions, which were also in the mouse cells. Statistical analysis showed that the expression of the uvp1 and uvp2 regions significantly increased (P less than 0.01) the survival upon exposure to UV light in mouse cells and bacteria. These results might suggest the presence of an inducible repair response to DNA damage in mouse LTA cells.

A Novel Approach to DNA Damage Assessments: Measurement of the Thymine Glycol Lesion

2006 ◽  
Vol 165 (4) ◽  
pp. 438-444 ◽  
Author(s):  
Douglas T. Bailey ◽  
Han-Chun C. DeFedericis ◽  
Kellee F. Greene ◽  
Herbert Iijima ◽  
Edwin E. Budzinski ◽  
...  
Keyword(s):  
Dna Damage ◽  
Thymine Glycol ◽  
Novel Approach

scholarly journals Estimation of oxidative DNA damage in man from urinary excretion of repair products.

1998 ◽  
Vol 45 (1) ◽  
pp. 133-144 ◽  
Author(s):  
S Loft ◽  
H E Poulsen
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Nuclear Dna ◽  
Inflammatory Diseases ◽  
Average Rate ◽  
Energy Restriction ◽  
Dna Lesions ◽  
Water Soluble ◽  
Nucleotide Synthesis ◽  
Thymine Glycol

DNA is constantly damaged and repaired in living cells. The repair products of the oxidative DNA lesions, i.e. oxidised nucleosides and bases, are poor substrates for the enzymes involved in nucleotide synthesis, are fairly water soluble, and generally excreted into the urine without further metabolism. Among the possible products, 8-oxo-2'-deoxyguanosine, 8-oxoguanine, thymine glycol, thymidine glycol and, 5-hydroxymethyluracil have so far been identified in urine. It should be emphasised that the excretion of the repair products in urine represents the average rate of damage in the total body whereas the level of oxidised bases in nuclear DNA is a concentration measurement in that specific tissue/cells in the moment of sampling. The rate of oxidative DNA modifications has been studied in humans by means of the repair products as urinary biomarkers, particularly with respect to 8-oxo-2'-deoxyguanosine. The data obtained so far indicate that the important determinants of the oxidative damage rate include tobacco smoking, oxygen consumption and some inflammatory diseases whereas diet composition, energy restriction and antioxidant supplements have but a minimal influence, possibly with the exception of yet unidentified phytochemicals, e.g. from cruciferous vegetables. The data are consistent with the experimentally based notion that oxidative DNA damage is an important mutagenic and apparently carcinogenic factor. However, the proof of a causal relationship in humans is still warranted. In the future the use of biomarkers may provide this evidence and allow further investigations on the qualitative and quantitative importance of oxidative DNA modification and carcinogenesis in man, as well as elucidate possible preventive measures.

scholarly journals Processing of thymine glycol in a clustered DNA damage site: mutagenic or cytotoxic

2009 ◽  
Vol 37 (13) ◽  
pp. 4430-4440 ◽  
Author(s):  
Sophie Bellon ◽  
Naoya Shikazono ◽  
Siobhan Cunniffe ◽  
Martine Lomax ◽  
Peter O’Neill
Keyword(s):  
Dna Damage ◽  
Damage Site ◽  
Thymine Glycol ◽  
Clustered Dna Damage

scholarly journals Assay for reactive oxygen species-induced DNA damage: measurement of the formamido and thymine glycol lesions

1999 ◽  
Vol 1454 (1) ◽  
pp. 80-88 ◽  
Author(s):  
Alexander E. Maccubbin ◽  
Helen B. Patrzyc ◽  
Noreen Ersing ◽  
Edwin E. Budzinski ◽  
Jean B. Dawidzik ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Thymine Glycol

Cellular response to DNA damage is enhanced by the pR plasmid in mouse cells and in Escherichia coli

1986 ◽  
Vol 6 (2) ◽  
pp. 586-592
Author(s):  
L Marcucci ◽  
F Gigliani ◽  
P A Battaglia ◽  
R Bosi ◽  
E Sporeno ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Statistical Analysis ◽  
Cellular Response ◽  
Regulatory Mechanism ◽  
Uv Light ◽  
Transformed Cells ◽  
Insertion Mutagenesis ◽  
Mouse Cells ◽  
Inducible Repair

The pR plasmid, which enhances the survival of Escherichia coli C600 exposed to UV light by induction of the SOS regulatory mechanism, showed the same effect when it transformed mouse LTA cells (tk-, aprt-). With Tn5 insertion mutagenesis which inactivates UV functions in the pR plasmid, we recognized two different regions of the plasmid, uvp1 and uvp2. These pR UVR- mutants exhibited the same effect in LTA transformed cells, demonstrating that resistance to UV light, carried by the pR plasmid, was really due to the expression of these two regions, which were also in the mouse cells. Statistical analysis showed that the expression of the uvp1 and uvp2 regions significantly increased (P less than 0.01) the survival upon exposure to UV light in mouse cells and bacteria. These results might suggest the presence of an inducible repair response to DNA damage in mouse LTA cells.

Inducible repair of oxidative DNA damage in Escherichia coli

Nature ◽  
1983 ◽  
Vol 304 (5925) ◽  
pp. 466-468 ◽  
Author(s):  
Bruce Demple ◽  
James Halbrook
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Inducible Repair

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

Blood ◽  
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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