The effects of ionizing radiation on structure and function of DNA

George, A.M.; Cramp, W.A.

doi:10.1016/0079-6107(87)90012-5

Cited by 29 publications

(9 citation statements)

References 206 publications

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“…Methods which use alkaline lysis and denaturation of DNA to detect DNA single-strand breaks, reviewed by Ahnstrom (1988) and George and Cramp (1987), are usually unable to discern differences in radiosensitivity between different cells or cell cycle phases . This is illustrated with monolayer/ spheroid data for alkaline sucrose gradient sedimentation ( Figure 1F), alkaline elution ( Figure 1G), and alkaline DNA precipitation ( Figure 1H) .…”

Section: Alkali Unwinding Is Influenced By Cell/ Nuclear Structurementioning

confidence: 99%

DNA Organization Affects Cellular Radiosensitivity and Detection of Initial DNA Strand Breaks

Olive

1992

International Journal of Radiation Biology

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Section: Alkali Unwinding Is Influenced By Cell/ Nuclear Structurementioning

confidence: 99%

DNA Organization Affects Cellular Radiosensitivity and Detection of Initial DNA Strand Breaks

Olive

1992

International Journal of Radiation Biology

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“…results with the comet assay indicate that the elevated chromosomal damage observed in treated AT cells is not due to a difference in the initial level of SS or DS DNA damage or in the rate of rejoining of strand breaks. Previous reports on the repair capacity of AT cells using X-irradition as the DNAdamaging agent suggest that the AT defect is not in SS DNA breakage and rejoining [Fornace and Little, 1980;Hariharan etal., 1981;Fornaceetal., 1986;Cantonietal., 19891, orin the initial level of DS DNA breakage [Coquerelle and Weibezahn, 1981;Coquerelle et al, 1987;Radford and Hodgson, 1990;Hittelman, 1992a, 1992bl. However, there may be a difference in the way AT cells process DS DNA damage [Coquerelle and Weibezahn, 1981;Coquerelle et al, 1987;George and Cramp, 1987;Debenham et al, 1987;Mozdarani and Bryant, 1989;Radford and Hodgson, 1990;Blocher et al, 1991;Hittelman, 1992a, 1992bl. Our results indicate no difference in rejoining rate, or extent of rejoining. Since heavily damaged cells can be excluded from analysis, rejoining rates using the comet assay may be a more accurate indicator of repair.…”

Section: Acknowledgmentsmentioning

confidence: 99%

Response of fibroblast cultures from ataxia‐telangiectasia patients to reactive oxygen species generated during inflammatory reactions

Ward

Olive²,

Burr

et al. 1994

Environ and Mol Mutagen

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Cells from patients with ataxia-telangiectasia (AT) are more sensitive than cells from normal individuals to a number of compounds which induce DNA damage via oxygen-derived free radical attack. We tested the hypothesis that AT cells would show a sensitivity to reactive oxygen species (ROS) generated by activated inflammatory cells. AT cells were exposed to neutrophils activated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or to xanthine/xanthine oxidase (X/XO), an enzyme system which generates superoxide and hydrogen peroxide. Induced micronuclei (MN) frequencies (corrected for spontaneous MN frequencies) were significantly higher in AT cell cultures than in cultures from normal individuals (comparison of MN frequencies of AT vs. normal cultures: for treatment with activated neutrophils, P = 0.003; for X/XO, P = 0.05). The comet assay was used to determine whether the elevated chromosomal damage in the treated AT cells was due to a difference in strand breakage or its rejoining. X/XO treatment was used in studies of single-stranded (SS) DNA breakage, and X-ray treatment for double-stranded (DS) DNA damage. AT and normal cells showed no significant differences in the initial levels of SS (P = 0.29) or DS (P = 0.91) DNA damage. Likewise, they exhibited similar rejoining kinetics (rejoining half-time for SS = 10 min, for DS = 30 min). These data support the involvement of the AT loci in determining a cell's ability to deal with oxidative stress, although the mechanism underlying this effect has yet to be resolved. The data also suggest that AT patients are at elevated risk of sustaining DNA damage in tissues undergoing inflammatory reactions.

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“…Determination of the Stereoisomer Form of the Thymine GlycolPermanganate oxidation of thymine has been shown to yield only the two cis-isomers (4,28). The determination of the stereochemistry of the cis-thymine glycol produced by the oxidation of single stranded DNA was determined by HPLC and confirmed by NMR.…”

Section: Methodsmentioning

confidence: 99%

“…These activities form the basis for using radiation in chemotherapy, and the research in this area has been frequently reviewed (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Since the mid-1950s there have been studies on the effects of ionizing radiation on the chemical integrity of DNA (4,5,7,9,14). Ionizing radiation can induce a number of types of damage to DNA including single and double strand breaks, oxidation of the purine and pyrimidine bases, and cross-linking of DNA with proteins.…”

mentioning

confidence: 99%

Structure of a Duplex DNA Containing a Thymine Glycol Residue in Solution

Kung

Bolton

1997

Journal of Biological Chemistry

105

114

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Oxidative stress, ionizing radiation, and other events can induce the oxidation of the thymine in DNA to thymine glycol. The presence of thymine glycol can have significant biological consequences, and there are specific repair enzymes for thymine glycol in a wide range of organisms. The structure of a duplex DNA containing a single thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine) has been determined by the combined use of NMR and restrained molecular dynamics. The duplex of d(C 1 G 2 C 3 G 4 A 5 Tg 6 A 7 C 8 G 9 C 10 C 11 ) paired with d(G 22 C 21 G 20 -C 19 T 18 A 17 T 16 G 15 C 14 G 13 G 12 ), with Tg indicating thymine glycol, has been used for these studies. The structure shows that the thymine glycol induces a significant, localized structural change with the thymine glycol largely extrahelical. This structural information is consistent with the biological consequences of thymine glycol in DNA. This structure is compared with that of a DNA duplex with an abasic site in the same sequence context.Damage to DNA can occur by the spontaneous deamination of cytosine to uracil and through the action of alkylating agents, oxidants, drugs, and toxins, ionizing radiation, and other modes of action (1-3). The exposure of DNA in cells bound to proteins as a solid or free in solution to ionizing radiation or to oxidative stress can lead to the conversion of thymine to thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine). Approximately 10 -20% of the damage to DNA induced by ionizing radiation, including that used to treat tumors, is the result of thymine base oxidation and fragmentation. These products can also be produced by oxidative stress. In addition, the importance of damaged DNA as a control on the cell cycle is increasingly becoming a focus of research efforts so that the effects of damaged thymines on the structures, stabilities, dynamics, and interactions of DNA are of interest.It has been known for several decades that ionizing radiation can stop the reproduction of cells as well as kill cells. These activities form the basis for using radiation in chemotherapy, and the research in this area has been frequently reviewed (1-13). Since the mid-1950s there have been studies on the effects of ionizing radiation on the chemical integrity of DNA (4,5,7,9, 14). Ionizing radiation can induce a number of types of damage to DNA including single and double strand breaks, oxidation of the purine and pyrimidine bases, and cross-linking of DNA with proteins. Radiation-generated oxidants are thought to react with thymine to lead to the formation of thymine glycol, thymine peroxide, thymine hydroperoxide, and other oxidized forms of the base. Some of these oxidized forms of thymine subsequently react further to form urea. Some of the same types of damage also occurs to DNA during oxidative stress (5,15,16).The damage to the thymine bases in DNA is of special interest because the major forms of damaged thymine are known; thymine is the most easily oxidized base, and many of the biological consequences of damaged thymines a...

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The effects of ionizing radiation on structure and function of DNA

Cited by 29 publications

References 206 publications

DNA Organization Affects Cellular Radiosensitivity and Detection of Initial DNA Strand Breaks

DNA Organization Affects Cellular Radiosensitivity and Detection of Initial DNA Strand Breaks

Response of fibroblast cultures from ataxia‐telangiectasia patients to reactive oxygen species generated during inflammatory reactions

Structure of a Duplex DNA Containing a Thymine Glycol Residue in Solution

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