Double-strand breaks, induction

Olive PL, Banath JP, MacPhail HS (1994) Lack of a correlation between radiosensitivity and DNA double-strand break induction or rejoining in six human tumor cell lines. Cancer Res 54 3939 3946... 

Whitaker SJ, McMillan TJ (1992) Oxygen effect for DNA double-strand break induction determined by pulsed-field gel electrophoresis. Int J Radiat Biol 61 29-41... 

The outcome of rapid radiation chemical processes in mammalian cells is to cause a variety of longer-Hved physical alterations in the DNA. Of these, double-strand breaks (DSBs) appear to be most frequently involved in cell killing if not correctly repaired. In general, thiols protect against DSB induction in proportion to their effect on cell killing (7), although there are exceptions (8). 

Gregoire V, Beauduin M, Bruniaux M, et al. Radiosensitization of mouse sarcoma cells by fludarabine (F-ara-A) or gemcitabine (dFdC), two nucleoside analogues, is not mediated by an increased induction or a repair inhibition of DNA double-strand breaks as measured by pulsed-field gel electrophoresis. Int JRadiat Biol 1998 73(5) 511-520. 

Figure 1 Action spectra for the induction of single strand break (ssb, open circle) and double strand break (dsb, closed circle) in dry plasmid DNA. Ratio of the cross section of ssb against dsb is also shown in lower panel. Solid line is reconstructed absorption cross section of the plasmid. (From Refs. 12, 13, 22, and 25.)...

Figure 5 Individual examples of simulated sites of damage induced by 3.2 MeV alpha particles in DNA. In each example, the outer and inner rows represent the sugar-phosphate moieties and the pairs of bases, respectively, with single base pair resolution (dots). An x or H represent energy deposition or reaction of hydroxyl radical leading to induction of a single strand break or base damage. A indicates hit sites that did not lead to strand breaks (SB) or base damage (BD). Nomenclature no strand break (No SB) single strand break (SSB), (SSB ), (2SSB) double strand break (DSB), (DSB+), (DSB + ).

It was surmised that X-ray-induced base damage would lead mostly to recessive lesions and that the significant damage in cells other than haploids was, therefore, of a different nature. In due course, it was shown that the principal agent of lethality was the formation of double-strand breaks, since in strains defective in doublestrand break repair, inactivation and the induction of double-strand breaks were in a 1 1 ratio (Ho, 1975). 

Ho, K. (1975). Induction of double-strand breaks by X-rays in a radiosensitive strain of yeast. Mutation Res. 30, 327-334. 

Valota A, Ballarini F, Friedland W, Jacob P, Ottolenghi A, Paretzke HG (2003) Modelling study on the protective role of OH radical scavengers and DNA higher-order structures in induction of single and double strand breaks by gamma-radiation. Int J Radiat Biol 79 643-653... 

Folkard M, Prise KM, Vojnovic B, Brocklehurst B, Michael BD (2000) Critical energies for ssb and dsb induction in plasmid DNA by vacuum-UV photons an arrangement for irrdiating dry or hydrated DNA with monochromatic photons. Int J Radiat Biol 76 763-771 Folkard M, Prise KM, Turner CJ, Michael BD (2002) The production of single strand and double strand breaks in aqueous solution by vacuum UV photons below 10 eV. Radiat Prot Dosim 99 147-149 FoxRA, Fielden EM, SaporaO (1976) Yield of single-strand breaks in the DNA of E. coli 10 msec after irradiation. Int J Radiat Biol 29 391-394... 

Prise KM, Davies S, Michael BD (1989) Cell killing and DNA damage in Chinese hamster V79 cells treated with hydrogen peroxide. Int J Radiat Biol 55 583-592 Prise KM, Davies S, Michael BD (1992) A comparison of thechemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells. Int J Radiat Biol 61 721-728 Prise KM, Davies S, Michael BD(1993) Evidence for induction of DNA double-strand breaks at paired radical sites. Radiat Res 134 102-106... 

Figure 19-4. Open and solid symbols are the measured quantum yields (events per incident electron) for the induction of single strand breaks (SSB) (a) and double strand breaks (DSB) (b) in DNA films by 4-100 eV electron impact. The solid curves through the data are guides to the eye. The dotted curves symbolize general electron energy dependence of the cross sections for various nonresonant damage mechanisms, such as ionization cross sections, normalized here to the measured strand break yields at lOOeV...

Boudaiffa B, Hunting DJ, Cloutier P, Huels MA, Sanche L (2000). Induction of single- and double-strand breaks in plasmid DNA by 100-1500 eV electrons. Int J Radiat Biol 76 1209-1221. 

Vock, E.H., Lutz, W.K., Hormes, P., Hoffmann, H.D., and Vamvakass, A., Discrimination between genotoxi-city and cytotoxicity in the induction of DNA double-strand breaks in cells treated with etoposide, melphalan, cisplatin, potassium cyanide, Triton X-100, and gamma irradiation, Mutat. Res., 413, 83-94, 1998. 

Induction of double-strand breaks (Holbeck and Strathern, 1999). 

Genetic variation can be increased by an induction of double-stranded breaks in the DNA. The recombination/repair of DNA helix breaks can increase the frequency of nearby base substitutions and frame shifts. For example, V-region hypermutation in the antibody appears to involve the focused generation of DNA breaks at a specific stage in B-cell development. 

Fig. 3 Induction of DNA double-strand breaks by single and dual agent PLN formulations.

A) MDA435/LCC6/WT cells were treated with dmg-PLN formulation containing 1.2 xM DOX and 0.6 )iM MMC for 1 h prior to processing by the TUNEL assay for DNA doublestrand break induction. Data are the mean standard deviations of three independent trials. Significant increase in DNA double-strand breaks relative to drug-free control (p<0.05). 

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