The Influence of Oxygen on the Survival and Yield of DNA Double-strand Breaks in Irradiated Yeast Cells

Frankenberg-Schwager, M.; Frankenberg, D.; Blöcher, Detlef; Adamczyk, C.

doi:10.1080/09553007914551031

Cited by 37 publications

(8 citation statements)

References 13 publications

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“…It has already been reported that in yeast the OER for induced dsb is 1.3 for e-particles (Frankenberg et al 1981) and 3.0 for sparsely ionizing 30 MeV electrons (Frankenberg-Schwager et al 1979). These data are in agreement with the low OERs generally observed for radiobiological endpoints at high LET.…”

Section: Discussionsupporting

confidence: 84%

Evidence against the ?oxygen-in-the-track? hypothesis as an explanation for the radiobiological low oxygen enhancement ratio at high linear energy transfer radiation

Frankenberg-Schwager¹,

Frankenbergt²,

Harbich

et al. 1994

Radiat Environ Biophys

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Oxygen sensitizes cells toward the effect of ionizing radiation. This sensitization, quantified by the oxygen enhancement ratio (OER), decreases with increasing ionization density or linear energy transfer (LET) of the radiation applied. One explanation for the decreased OER at high LET offers the "oxygen-in-the-track" hypothesis. It claims that oxygen is produced in the track of densely ionizing particles providing an oxic microenvironment around the relevant cellular target molecules, even if cells are exposed under anoxic atmospheric conditions. Experimental evidence is presented against this hypothesis. It is based on the different kinetic pattern of DNA double-strand-break rejoining observed in yeast cells exposed under oxic or anoxic conditions to 3.5 MeV alpha-particles.

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Section: Discussionsupporting

confidence: 84%

Evidence against the ?oxygen-in-the-track? hypothesis as an explanation for the radiobiological low oxygen enhancement ratio at high linear energy transfer radiation

Frankenberg-Schwager¹,

Frankenbergt²,

Harbich

et al. 1994

Radiat Environ Biophys

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“…This strain, originally constructed by Brendel and F~ith (1974), is homozygous for the templ-3 marker conferring auxotropy for 2'-deoxythymidine (5'-dTMP) (Frankenberg-Schwager et al 1979). It is a petite lacking mitochondrial DNA and was generously given to us by Dr. M. Frankenberg-Schwager, G6ttingen, formerly GSF, Frankfurt.…”

Section: Yeast Strainmentioning

confidence: 99%

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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“…This observation suggests that DSB induction per base pair is approximately the same in the lower and higher eukaryotes. In yeast cells irradiated by 30 MeV electrons, the initial DSB yield per cell increases linearly with dose up to at least 2400 Gy under fully aerobic (100% O 2 ) conditions and up to at least 1500 Gy under maximally hypoxic conditions (17). The production of Fpg (oxidized purine), Endo III (oxidized pyrimidine) and Endo IV (abasic) non-DSB clusters is also proportional to absorbed dose for low-and high-LET radiations from at least 0.05 Gy up to 30 Gy (6,(18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Effects of Radiation Quality and Oxygen on Clustered DNA Lesions and Cell Death

et al. 2011

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Radiation quality and cellular oxygen concentration have a substantial impact on DNA damage, reproductive cell death and, ultimately, the potential efficacy of radiation therapy for the treatment of cancer. To better understand and quantify the effects of radiation quality and oxygen on the induction of clustered DNA lesions, we have now extended the Monte Carlo Damage Simulation (MCDS) to account for reductions in the initial lesion yield arising from enhanced chemical repair of DNA radicals under hypoxic conditions. The kinetic energy range and types of particles considered in the MCDS have also been expanded to include charged particles up to and including (56)Fe ions. The induction of individual and clustered DNA lesions for arbitrary mixtures of different types of radiation can now be directly simulated. For low-linear energy transfer (LET) radiations, cells irradiated under normoxic conditions sustain about 2.9 times as many double-strand breaks (DSBs) as cells irradiated under anoxic conditions. New experiments performed by us demonstrate similar trends in the yields of non-DSB (Fpg and Endo III) clusters in HeLa cells irradiated by γ rays under aerobic and hypoxic conditions. The good agreement among measured and predicted DSBs, Fpg and Endo III cluster yields suggests that, for the first time, it may be possible to determine nucleotide-level maps of the multitude of different types of clustered DNA lesions formed in cells under reduced oxygen conditions. As particle LET increases, the MCDS predicts that the ratio of DSBs formed under normoxic to hypoxic conditions by the same type of radiation decreases monotonically toward unity. However, the relative biological effectiveness (RBE) of higher-LET radiations compared to (60)Co γ rays (0.24 keV/μm) tends to increase with decreasing oxygen concentration. The predicted RBE of a 1 MeV proton (26.9 keV/μm) relative to (60)Co γ rays for DSB induction increases from 1.9 to 2.3 as oxygen concentration decreases from 100% to 0%. For a 12 MeV (12)C ion (681 keV/μm), the 'predicted RBE for DSB induction increases from 3.4 (100% O(2)) to 9.8 (0% O(2)). Estimates of linear-quadratic (LQ) cell survival model parameters (α and β) are closely correlated to the Monte Carlo-predicted trends in DSB induction for a wide range of particle types, energies and oxygen concentrations. The analysis suggests α is, as a first approximation, proportional to the initial number of DSBs per cell, and β is proportional to the square of the initial number of DSBs per cell. Although the reported studies provide some evidence supporting the hypothesis that DSBs are a biologically critical form of clustered DNA lesion, the induction of Fpg and Endo III clusters in HeLa cells irradiated by γ rays exhibits similar trends with oxygen concentration. Other types of non-DSB cluster may still play an important role in reproductive cell death. The MCDS captures many of the essential trends in the formation of clustered DNA lesions by ionizing radiation and provides useful information to probe the mu...

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The Influence of Oxygen on the Survival and Yield of DNA Double-strand Breaks in Irradiated Yeast Cells

Cited by 37 publications

References 13 publications

Evidence against the ?oxygen-in-the-track? hypothesis as an explanation for the radiobiological low oxygen enhancement ratio at high linear energy transfer radiation

Evidence against the ?oxygen-in-the-track? hypothesis as an explanation for the radiobiological low oxygen enhancement ratio at high linear energy transfer radiation

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

Effects of Radiation Quality and Oxygen on Clustered DNA Lesions and Cell Death

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