No dose-dependence of DNA double-strand break misrejoining following alpha-particle irradiation
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No dose-dependence of DNA double-strand break misrejoining following alpha-particle irradiation. / Kühne, M; Rothkamm, K; Löbrich, M.
In: INT J RADIAT BIOL, Vol. 76, No. 7, 07.2000, p. 891-900.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - No dose-dependence of DNA double-strand break misrejoining following alpha-particle irradiation
AU - Kühne, M
AU - Rothkamm, K
AU - Löbrich, M
PY - 2000/7
Y1 - 2000/7
N2 - PURPOSE: To investigate whether an explanation for the high effectiveness of densely ionizing radiation with regard to complex biological endpoints can be derived from measurements of radiation-induced double-strand break (DSB) misrejoining.MATERIALS AND METHODS: Misrejoining of radiation-induced DSB in normal human fibroblasts was determined by comparing hybridization analysis of large restriction fragments as a measure for correct rejoining, with results from a conventional pulsed-field gel electrophoresis technique (FAR) that measures total DSB rejoining. In order to investigate DSB misrejoining at doses for which chromosome aberration data are available, a dose fractionation protocol was applied so that the number of DSB at any given timepoint was low but the cumulative amount of misrejoined DSB sufficient for detection and precise quantitation.RESULTS AND CONCLUSION: After an acute 80Gy alpha-particle exposure and a repair incubation period of 24 h, 50% of all initially induced DSB were misrejoined, in agreement with data obtained for X-rays. X-irrradiation with 16 x 5 Gy, 8 x 10 Gy, 4 x 20 Gy, or 2 x 40 Gy and repair incubation of 24 h following each individual dose fraction was recently reported to yield misrejoining frequencies that strongly decrease with increasing fractionation (Löbrich et al. 2000; Genes, Chromosomes and Cancer, 27, 59-68). In the present study, constant misrejoining frequencies of 50% were observed after alpha-particle exposure with the same fractionation protocol. This difference between alpha-particles and X-rays is in accordance with the high biological effectiveness of densely ionizing radiation and provides a direct link between misrejoining of DSB and cytologically visible exchange aberrations. Further evidence suggests that if the same dose range is compared, the number of misrejoined DSB exceeds the number of microscopically visible aberrations by an order of magnitude for both radiation types, probably reflecting the high resolution of the hybridization approach compared with cytological techniques.
AB - PURPOSE: To investigate whether an explanation for the high effectiveness of densely ionizing radiation with regard to complex biological endpoints can be derived from measurements of radiation-induced double-strand break (DSB) misrejoining.MATERIALS AND METHODS: Misrejoining of radiation-induced DSB in normal human fibroblasts was determined by comparing hybridization analysis of large restriction fragments as a measure for correct rejoining, with results from a conventional pulsed-field gel electrophoresis technique (FAR) that measures total DSB rejoining. In order to investigate DSB misrejoining at doses for which chromosome aberration data are available, a dose fractionation protocol was applied so that the number of DSB at any given timepoint was low but the cumulative amount of misrejoined DSB sufficient for detection and precise quantitation.RESULTS AND CONCLUSION: After an acute 80Gy alpha-particle exposure and a repair incubation period of 24 h, 50% of all initially induced DSB were misrejoined, in agreement with data obtained for X-rays. X-irrradiation with 16 x 5 Gy, 8 x 10 Gy, 4 x 20 Gy, or 2 x 40 Gy and repair incubation of 24 h following each individual dose fraction was recently reported to yield misrejoining frequencies that strongly decrease with increasing fractionation (Löbrich et al. 2000; Genes, Chromosomes and Cancer, 27, 59-68). In the present study, constant misrejoining frequencies of 50% were observed after alpha-particle exposure with the same fractionation protocol. This difference between alpha-particles and X-rays is in accordance with the high biological effectiveness of densely ionizing radiation and provides a direct link between misrejoining of DSB and cytologically visible exchange aberrations. Further evidence suggests that if the same dose range is compared, the number of misrejoined DSB exceeds the number of microscopically visible aberrations by an order of magnitude for both radiation types, probably reflecting the high resolution of the hybridization approach compared with cytological techniques.
KW - Alpha Particles
KW - Cells, Cultured
KW - DNA/radiation effects
KW - DNA Damage
KW - DNA Repair
KW - Dose-Response Relationship, Radiation
KW - Humans
KW - X-Rays
U2 - 10.1080/09553000050050909
DO - 10.1080/09553000050050909
M3 - SCORING: Journal article
C2 - 10923613
VL - 76
SP - 891
EP - 900
JO - INT J RADIAT BIOL
JF - INT J RADIAT BIOL
SN - 0955-3002
IS - 7
ER -