Relative biological effectiveness of high linear energy transfer α-particles             for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive             cell death in SW-1573 lung tumour cells.
Ionizing radiation-induced foci (IRIF) of DNA repair-related proteins accumulated             at DNA double-strand break (DSB) sites have been suggested to be a powerful biodosimetric             tool. However, the relationship between IRIF induction and biologically relevant             endpoints, such as cell death and formation of chromosome rearrangements is less             clear, especially for high linear energy transfer (LET) radiation. It is thus             not sufficiently established whether IRIF are valid indicators of biological effectiveness             of the various radiation types. This question is more significant in light of             the recent advancements in light ion-beam and radionuclide therapy. Dose-effect             relationships were determined for the induction of DNA-DSBs, chromosome aberrations             and reproductive cell death in cultured SW-1573 cells irradiated with γ-rays from             a Cs-137 source or with α-particles from an Am-241 source. Values of relative             biological effectiveness (RBE) of the high LET α-particles were derived for these             effects. DNA-DSB were detected by scoring of γ-H2AX foci, chromosome aberrations             by fragments and translocations using premature chromosome condensation and cell             survival by colony formation. Analysis of dose-effect relations was based on the             linear-quadratic model. Except for the survival curves, for other effects no significant             contribution was derived of the quadratic term in the range of doses up to 2 Gy             of γ-rays. Calculated RBE values derived for the linear component of dose-effect             relations for γ-H2AX foci, cell reproductive death, chromosome fragments and colour             junctions are 1.0±0.3, 14.7±5.1, 15.3±5.9 and 13.3±6.0, respectively. RBE values             calculated at a certain biological effect level are 1, 4, 13 and 13, respectively.             The RBE values derived from the LQ model are preferred as they are based on clinically             relevant doses. The results show that with low LET radiation only a small fraction             of the numerous DNA-DSBs yield chromosome damage and reproductive cell death.             It is concluded that many of the chromosomal aberrations detected by premature             chromosome condensation do not cause reproductive cell death. Furthermore, RBE             values for DNA-DSB detectable by γ-H2AX foci shortly after irradiation, provide             no information relevant to applications of high LET radiation in radiotherapy.             The RBE values of chromosome aberrations assessed by premature chromosome condensation             are close to the value for reproductive cell death. This suggests possible relevance             to assess RBE values for radiotherapy with high LET ions.
Department of Radiation Oncology, Laboratory for Experimental Oncology and Radiobiology (LEXOR), Centre for Experimental Molecular Medicine, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. n.a.franken@amc.uva.nl
Nicolaas A P
NA
Franken
Suzanne
S
Hovingh
Rosemarie
R
Ten Cate
Przemek
P
Krawczyk
Jan
J
Stap
Ron
R
Hoebe
Jacob
J
Aten
Gerrit W
GW
Barendsen
D000512:Alpha Particles / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D016923:Cell Death / Q000528:radiation effects*; D002455:Cell Division / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000627:therapeutic use; D006801:Humans; D018499:Linear Energy Transfer / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D012062:Relative Biological Effectiveness
D004273:DNA, Neoplasm