Heavy Ion-induced DNA Double-strand Breaks in Yeast

Akpa, T. C.; Weber, Klaus-Josef; Schneider, Elisabeth; Kiefer, Jürgen; Frankenberg-Schwager, M.; Harbich, R.; Frankenberg, D.

doi:10.1080/09553009214552121

Cited by 32 publications

(8 citation statements)

References 24 publications

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“…Whether this represents differences in the biological systems studied or the methods used still requires elucidation. However, there appears to be some agreement, irrespective of the system studied, in the finding of a drastic reduction in the efficiency of heavy ions with LET higher than 200-300 keV/gm for DSB induction (Akpa et al 1992;Heilmann et al 1993;Weber and Flentje 1993). On the whole, the question as to how the cell-killing RBE-LET relationship compares with that for DSB induction has attracted considerable interest since its clarification could throw more light on several problems such as whether the shoulders found in survival curves are primar-ily due to cellular repair or radiochemically dependent processes.…”

Section: Introductionmentioning

confidence: 70%

“…Experimental details of both methods have been published (Akpa et al 1992;L6brich et al 1993). While the first one is a well-known standard procedure, the second is rather new and deserves a few words of explanation.…”

Section: Determination Of Induced Double-strand Breaksmentioning

confidence: 99%

“…For particulate radiation, the yield of DSB s per unit dose has been found to increase with LET up to about 150 keV/gm in yeast cells (Frankenberg et al 1981;Akpa et al 1992;L6brich et al 1993) as well as in earlier studies with mammalian cells (Kampf 1982;Kampf and Eichhorn 1983). Such a LET-RBE (relative biological effectiveness) relationship is consistent with computational Monte-Carlo simulations Chatterjee and Holley 1991).…”

Section: Introductionmentioning

confidence: 95%

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Heavy ion-induced DNA double-strand breaks with yeast as a model system

Ikpeme

Löbrich

Akpa

et al. 1995

Radiat Environ Biophys

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Cells of diploid yeast, Saccharomyces cerevisiae, were exposed to a variety of energetic heavy ions (provided by the UNILAC facility at the Gesellschaft für Schwerionenforschung, GSI), 241Am alpha-particles and 80-keV x-rays after which they were assessed for DNA double-strand breaks (DSB) using either the neutral sedimentation or the pulsed-field gel electrophoresis (PFGE) technique. Both yielded comparable results. The DSB production cross-sections are compared with inactivation studies performed for the same cells under identical conditions. The measurements show that with lighter ions DSB induction cross-sections increase with linear energy transfer (LET), but the situation is less clear with the heavier ions. A close parallelism was found between DSB induction and cell inactivation in these yeast cells.

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Section: Introductionmentioning

confidence: 70%

Section: Determination Of Induced Double-strand Breaksmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Heavy ion-induced DNA double-strand breaks with yeast as a model system

Ikpeme

Löbrich

Akpa

et al. 1995

Radiat Environ Biophys

Self Cite

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“…The general finding is an increase in yield with LET up to a few hundred keV/4m and a subsequent decline (4,8,(18)(19)(20)(21). A particularly complete set of data for the high-LET range is available for the yeast system (20).…”

Section: Introductionmentioning

confidence: 97%

DNA Double-Strand Breaks Induced by High-Energy Neon and Iron Ions in Human Fibroblasts. I. Pulsed-Field Gel Electrophoresis Method

Cooper¹,

Rydberg²,

Löbrich³

1994

Radiation Research

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The relative effectiveness of high-energy neon and iron ions for the production of DNA double-strand breaks was measured in one transformed and one nontransformed human fibroblast cell line using pulsed-field gel electrophoresis. The DNA released from the gel plug (fraction of activity released: FAR) as well as the size distribution of the DNA entering the gel were used to compare the effects of the heavy-ion exposure with X-ray exposure. Both methods gave similar results, indicating similar distributions of breaks over megabase-pair distances for the heavy ions and the X rays. The relative biological effectiveness (RBE) compared to 225 kVp X rays of initially induced DNA double-strand breaks was found to be 0.85 for 425 MeV/u neon ions (LET 32 keV/microns) and 0.42-0.55 for 250-600 MeV/u iron ions (LET 190-350 keV/microns). Postirradiation incubation showed less efficient repair of breaks induced by the neon ions and the 600 MeV/u iron ions compared to X rays. Survival experiments demonstrated RBE values larger than one for cell killing by the heavy ions in parallel experiments (neon: RBE = 1.2, iron: RBE = 2.3-3.0, based on D10 values). It is concluded that either the initial yield of DNA double-strand breaks induced by the high-energy particles is lower than the yield for X rays, or the breaks induced by heavy ions are present in clusters that cannot be resolved with the technique used. These results are confirmed in the accompanying paper (M. Löbrich, B. Rydberg and P. Cooper, Radiat. Res. 139, 142-151, 1994).

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“…For DSB, however, which are due to multiple radical reactions, with increasing LET there is a higher probability of occurrence of "spurs" and "blobs" (Ward 1981) and thus a higher probability of DSB formation. This view is supported by the fact that the DSB/SSB ratio after irradiation of SV40 DNA in vitro increases up to threefold with increasing LET, but the RBE values strongly depend on the species of heavy ions (Roots et al 1990;Akpa et al 1992).…”

Section: Influence Of Let Of Dna Strand Breakage In Vivomentioning

confidence: 80%

Mechanisms of induction and repair of DNA double-strand breaks by ionizing radiation: Some contradictions

Hagen

1994

Radiat Environ Biophys

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The various aspects of formation and repair of radiation-induced double-strand breaks (DSB) are summarized. Concerning the structure of DSB found in irradiated cells, enzymatic and microdosimetric analysis hints at complex damage of the DNA structure at the position of a DSB. With increasing LET, the DSB damage may be more complex than that induced by low-LET irradiation. Most of the DSB are repaired in the irradiated cell; apparently the kinetics of DSB repair and the fraction of unrejoined DSB determine cell survival or cell death. We do not know the details of the complex machinery of DSB repair; certainly recombination processes are involved, but there are still contradictions between our current knowledge about the mechanisms of recombinational DSB repair and the observed kinetics.

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Heavy Ion-induced DNA Double-strand Breaks in Yeast

Cited by 32 publications

References 24 publications

Heavy ion-induced DNA double-strand breaks with yeast as a model system

Heavy ion-induced DNA double-strand breaks with yeast as a model system

DNA Double-Strand Breaks Induced by High-Energy Neon and Iron Ions in Human Fibroblasts. I. Pulsed-Field Gel Electrophoresis Method

Mechanisms of induction and repair of DNA double-strand breaks by ionizing radiation: Some contradictions

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