γ-H2AX and Phosphorylated ATM Focus Formation in Cancer Cells after Laser Plasma X Irradiation

Abstract The usefulness of laser plasma X-ray pulses for medical and radiation biological studies was investigated, and the effects of laser plasma X rays were compared with those of conventional sources such as a linear accelerator. A cell irradiation system was developed that used copper-Kα (8 keV) lines from an ultrashort high-intensity laser to produce plasma. The absorbed dose of the 8 keV laser plasma X-ray pulse was estimated accurately with Gafchromic® EBT film. When the cells were irradiated with approximately 2 Gy of laser plasma X rays, the circular regions on γ-H2AX-positive cells could be clearly identified. Moreover, the numbers of γ-H2AX and phosphorylated ataxia telangiectasia mutated (ATM) foci induced by 8 keV laser plasma X rays were comparable to those induced by 4 MV X rays. These results indicate that the laser plasma X ray source may be useful for radiation biology studies.

[1]  J. Mills,et al.  An assessment of GafChromic film for measuring 50 kV and 100 kV percentage depth dose curves , 2008, Physics in medicine and biology.

[2]  J M Rajyaguru,et al.  Direct ultrastructural imaging of macrophages using a novel x-ray contact microscopy. , 1999, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[3]  Fractionation in medium dose rate brachytherapy of cancer of the cervix. , 1996 .

[4]  Lu,et al.  Femtosecond studies of the presolvated electron: An excited state of the solvated electron? , 1990, Physical review letters.

[5]  A. Murtha,et al.  Low-Dose Radiation Hypersensitivity Is Associated With p 53-Dependent Apoptosis , 2004 .

[6]  T. Sun,et al.  Study on the measurement of properties of polycapillary X-ray lens , 2004 .

[7]  S Svanberg,et al.  Survival of mammalian cells exposed to ultrahigh dose rates from a laser-produced plasma x-ray source. , 1999, Radiology.

[8]  J. Friesner,et al.  Ionizing radiation-dependent gamma-H2AX focus formation requires ataxia telangiectasia mutated and ataxia telangiectasia mutated and Rad3-related. , 2005, Molecular biology of the cell.

[9]  M. Kado,et al.  X-ray micrography and imaging of Escherichia coli cell shape using laser plasma pulsed point x-ray sources. , 1997, Biophysical journal.

[10]  Forster,et al.  Yield optimization and time structure of femtosecond laser plasma kalpha sources , 2000, Physical review letters.

[11]  G. Schettino,et al.  A Focused Ultrasoft X-Ray Microbeam for Targeting Cells Individually with Submicrometer Accuracy , 2001, Radiation research.

[12]  Takamitsu A Kato,et al.  Levels of γ-H2AX Foci after Low-Dose-Rate Irradiation Reveal a DNA DSB Rejoining Defect in Cells from Human ATM Heterozygotes in Two AT Families and in Another Apparently Normal Individual , 2006, Radiation research.

[13]  M. Kastan,et al.  DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation , 2003, Nature.

[14]  A. Murtha,et al.  Low-dose radiation hypersensitivity is associated with p53-dependent apoptosis. , 2004, Molecular cancer research : MCR.

[15]  Bahram Parvin,et al.  Imaging Features that Discriminate between Foci Induced by High- and Low-LET Radiation in Human Fibroblasts , 2006, Radiation research.

[16]  Martin,et al.  Excess electrons in liquid water: First evidence of a prehydrated state with femtosecond lifetime. , 1987, Physical review letters.

[17]  E. Wilcox,et al.  Dosimetric verification of intensity modulated radiation therapy of 172 patients treated for various disease sites: comparison of EBT film dosimetry, ion chamber measurements, and independent MU calculations. , 2008, Medical dosimetry : official journal of the American Association of Medical Dosimetrists.

[18]  Michael Lichten,et al.  Distribution and Dynamics of Chromatin Modification Induced by a Defined DNA Double-Strand Break , 2004, Current Biology.

[19]  J. Fowler,et al.  Biologically effective doses in medium dose rate brachytherapy of cancer of the cervix. , 1997, Radiation oncology investigations.

[20]  J. Galvin,et al.  Radiochromic film dosimetry: recommendations of AAPM Radiation Therapy Committee Task Group 55. American Association of Physicists in Medicine. , 1998, Medical physics.

[21]  T. DeWeese,et al.  Evasion of Early Cellular Response Mechanisms following Low Level Radiation-induced DNA Damage* , 2004, Journal of Biological Chemistry.

[22]  Xiao-dan Liu,et al.  DNA-PKcs plays a dominant role in the regulation of H2AX phosphorylation in response to DNA damage and cell cycle progression , 2010, BMC Molecular Biology.

[23]  D. Hunting,et al.  Dosimetry of ultrasoft x-rays (1.5 keV AlKα) using radiochromatic films and colour scanners , 2003 .

[24]  Ivan V. Tomov,et al.  Efficient focusing of hard X-rays generated by femtosecond laser driven plasma , 2004 .

[25]  B. Ferreira,et al.  Evaluation of an Epson flatbed scanner to read Gafchromic EBT films for radiation dosimetry , 2009, Physics in medicine and biology.

[26]  Michael M. Murphy,et al.  ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks* , 2001, The Journal of Biological Chemistry.

[27]  P. Cavazzani,et al.  Fractionated stereotactic radiotherapy: a method to evaluate geometric and dosimetric uncertainties using radiochromic films. , 2009, Medical physics.

[28]  E. Rogakou,et al.  DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139* , 1998, The Journal of Biological Chemistry.

[29]  R. Ian Freshney,et al.  Culture of Animal Cells , 1983 .

[30]  Christopher P. J. Barty,et al.  Generation of hard x rays by ultrafast terawatt lasers , 2001 .

[31]  Hideaki Nakamura,et al.  DNA Repair Defect in AT Cells and their Hypersensitivity to Low-Dose-Rate Radiation , 2006, Radiation research.

[32]  M. Kado,et al.  High resolution X-ray micrography of live Candida albicans using laser plasma pulsed point X-ray sources. , 1997, Microbiology.

[33]  M. Butson,et al.  Radiochromic film dosimetry in water phantoms , 2001, Physics in medicine and biology.

[34]  E. Tanaka,et al.  Prospective study of HDR (192Ir) versus MDR (137Cs) intracavitary brachytherapy for carcinoma of the uterine cervix. , 2003, Brachytherapy.

[35]  P Lambin,et al.  Low-dose hypersensitivity: current status and possible mechanisms. , 2001, International journal of radiation oncology, biology, physics.

[36]  J. Fowler,et al.  Medium-dose-rate brachytherapy of cancer of the cervix: preliminary results of a prospectively designed schedule based on the linear-quadratic model. , 1999, International journal of radiation oncology, biology, physics.

[37]  Keiji Suzuki,et al.  Qualitative and Quantitative Analysis of Phosphorylated ATM Foci Induced by Low-Dose Ionizing Radiation , 2006, Radiation research.

[38]  S. C. Prasad,et al.  Laser-based microfocused x-ray source for mammography: feasibility study. , 1997, Medical physics.

[39]  Ryosuke Kodama,et al.  Effects of single-pulse (< or = 1 ps) X-rays from laser-produced plasmas on mammalian cells. , 2004, Journal of radiation research.

[40]  K. Kondo,et al.  Energy distribution of electrons ejected from a copper target in a femtosecond laser field of 1017 W/cm2 , 2004 .

[41]  E. Wilcox,et al.  Evaluation of GAFCHROMIC EBT film for Cyberknife dosimetry. , 2007, Medical physics.

[42]  B. Marples,et al.  Low-dose hyper-radiosensitivity: past, present, and future. , 2008, International journal of radiation oncology, biology, physics.

[43]  C. Kurtman,et al.  Early results of exclusive radiotherapy in advanced stage cervical carcinoma performed with reference to ICRU Report 38. , 2001, Radiation medicine.