Excision Repair of DNA damage formed by selected radiations
used in microbeam studies of low-dose radiation biology

Charged-particle microbeams are powerful tools in radiobiological research (for a review see [1]). Microbeam experiments have been conducted at the Radiological Research Accelerator Facility (RARAF) at Columbia University [2], the Gray Cancer Institute (formerly Gray Laboratory) microbeam [3, 4], and the Special Microbeam Utilization Research Facility (SMURF) at Texas A&M University. The SMURF at Texas A&M University was formerly located at the Pacific Northwest National Laboratory [5].  Information about repair outcomes for selected radiations can be found on the Monte Carlo Excision Repair (MCER) website (see also [6,7]).  The initial damage configurations used in the MCER simulation were generated using the fast Monte Carlo damage simulation (MCDS) algorithm [8, 9].

Columbia University

The Columbia University microbeam is designed to deliver helium or hydrogen ions with different energies that cover the range of LET from 30 to 220 keV/μm [2].  To date, all the studies that utilized this microbeam have been performed with 5.3 MeV α particles that have LET of approximately 90 keV/μm (for examples of studies with this microbeam system, see [10–21]).

• 5.3 MeV α particles (input file, output file)

Gray Cancer Institute

The Gray Cancer Institute microbeam was initially configured to irradiate cells with protons of energies <3.5 MeV [3].  Later a change has been made to also deliver ³He²⁺ ions.  The majority of studies performed using the Gray Cancer Institute microbeam used ³He²⁺ ions with LET of ~100 keV/μm [22–26].  1 and 3.2 MeV protons have also been utilized in some experiments [27, 28].

• 4 MeV α particles; equivalent to 100 keV/μm ³He²⁺ ions (input file, output file)

• 1 MeV protons (input file, output file)

• 3.2 MeV protons (input file, output file)

Texas A&M University (formerly located at PNNL)

The Texas A&M University microbeam is capable of producing α particles and protons with energies up to 6 MeV and up to 4 MeV respectively.  Also available is a 100 keV electron microbeam.  The predecessor of TAMU's microbeam, the microbeam at Pacific Northwest National Laboratory, has been applied in one study that utilized 3.2 MeV α particles [29].

• 3.2 MeV α particles  (input file, output file)

References

[1] Folkard M, Prise KM, Vojnovic B, Gilchrist S, Schettino G, Belyakov OV, Ozols A, Michael BD. The impact of microbeams in radiation biology. Nucl. Instr. Meth. Phys. Res. B 181 (2001) 426–430.

[2] Randers-Pehrson G, Geard CR, Johnson G, Elliston CD, Brenner DJ. The Columbia university single-ion microbeam. Radiat. Res. 156 (2001) 210–214. [PubMed]

[3] Folkard M, Vojnovic B, Prise KM, Bowey AG, Locke RJ, Schettino G, Michael BD. A charged-particle microbeam: I. Development of an experimental system for targeting cells individually with counted particles. Int. J. Radiat. Biol. 72 (1997) 375–385. [Abstract]

[4] Folkard M, Vojnovic B, Hollis KJ, Bowey AG, Watts SJ, Schettino G, Prise KM, Michael BD. A charged-particle microbeam: II. A single-particle micro-collimation and detection system. Int. J. Radiat. Biol. 72 (1997) 387–395. [PubMed]

[5] Braby LA, Brooks AL, Metting NF. Cellular effects of individual high-linear energy transfer particles and implications for tissue response at low doses. Radiat. Res. 148 (1997) S108–S114. [PubMed]

[6] Semenenko VA, Stewart RD, Ackerman EJ. Monte Carlo simulation of base and nucleotide excision repair of clustered DNA damage sites. I. Model properties and predicted trends. Radiat. Res. 164 (2005) 180-193. [PubMed] [HomePage]

[7] Semenenko VA, Stewart RD. Monte Carlo simulation of base and nucleotide excision repair of clustered DNA damage sites. II. Comparisons of model predictions to measured data. Radiat. Res. 164 (2005) 194-201. [PubMed] [HomePage]

[8] Semenenko VA, Stewart RD. A fast Monte Carlo algorithm to simulate the spectrum of DNA damages formed by ionizing radiation. Radiat. Res. 161 (2004) 451–457. [PubMed] [HomePage]

[9] Semenenko VA, Stewart RD. Fast Monte Carlo simulation of DNA damage formed by electrons and light ions. Phys. Med. Biol. 51 (2006) 1693–1706. [HomePage]

[10] Hei TK, Wu LJ, Liu SX, Vannais D, Waldren CA, Randers-Pehrson G. Mutagenic effects of a single and an exact number of α particles in mammalian cells. Proc. Natl. Acad. Sci. USA 94 (1997) 3765–3770. [PubMed]

[11] Miller RC, Randers-Pehrson G, Geard CR, Hall EJ, Brenner DJ. The oncogenic transforming potential of the passage of single α particles through mammalian cell nuclei. Proc. Natl. Acad. Sci. USA 96 (1999) 19–22. [PubMed]

[12] Wu LJ, Randers-Pehrson G, Xu A, Waldren CA, Geard CR, Yu Z, Hei TK. Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells. Proc. Natl. Acad. Sci. USA 96 (1999) 4959–4964. [PubMed]

[13] Zhou H, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ, Hei TK. Induction of a bystander mutagenic effect of alpha particles in mammalian cells. Proc. Natl. Acad. Sci. USA 97 (2000) 2099–2104. [PubMed]

[14] Zhou H, Suzuki M, Randers-Pehrson G, Vannais D, Chen G, Trosko JE, Waldren CA, Hei TK. Radiation risk to low fluences of α particles may be greater than we thought. Proc. Natl. Acad. Sci. USA 98 (2001) 14410–14415. [PubMed]

[15] Sawant SG, Randers-Pehrson G, Geard CR, Brenner DJ, Hall EJ. The bystander effect in radiation oncogenesis: I. Transformation in C3H 10T½ cells in vitro can be initiated in the unirradiated neighbors of irradiated cells. Radiat. Res. 155 (2001) 397–401. [PubMed]

[16] Sawant SG, Randers-Pehrson G, Metting NF, Hall EJ. Adaptive response and the bystander effect induced by radiation in C3H 10T½ cells in culture. Radiat. Res. 156 (2001) 177–180. [PubMed]

[17] Sawant SG, Zheng W, Hopkins KM, Randers-Pehrson G, Lieberman HB, Hall EJ. The radiation-induced bystander effect for clonogenic survival. Radiat. Res. 157 (2002) 361–364. [PubMed]

[18] Zhou H, Randers-Pehrson G, Geard CR, Brenner DJ, Hall EJ, Hei TK. Interaction between radiation-induced adaptive response and bystander mutagenesis in mammalian cells. Radiat. Res. 160 (2003) 512–516. [PubMed]

[19] Mitchell SA, Randers-Pehrson G, Brenner DJ, Hall EJ. The bystander response in C3H 10T(1/2) cells: the influence of cell-to-cell contact. Radiat. Res. 161 (2004) 397–401. [PubMed]
 

[20] Mitchell SA, Marino SA, Brenner DJ, Hall EJ. Bystander effect and adaptive response in C3H 10T(1/2) cells. Int. J. Radiat. Biol. 80 (2004) 465–472. [PubMed]

[21] Ponnaiya B, Jenkins-Baker G, Brenner DJ, Hall EJ, Randers-Pehrson G, Geard CR. Biological responses in known bystander cells relative to known microbeam-irradiated cells. Radiat. Res. 162 (2004) 426–432. [PubMed]

[22] Prise KM, Belyakov OV, Folkard M, Michael BD. Studies of bystander effects in human fibroblasts using a charged particle microbeam. Int. J. Radiat. Biol. 74 (1998) 793–798. [PubMed]

[23] Kadhim MA, Marsden SJ, Goodhead DT, Malcolmson AM, Folkard M, Prise KM, Michael BD. Long-term genomic instability in human lymphocytes induced by single-particle irradiation. Radiat. Res.155 (2001) 122–126. [PubMed]

[24] Belyakov OV, Malcolmson AM, Folkard M, Prise KM, Michael BD. Direct evidence for a bystander effect of ionizing radiation in primary human fibroblasts. Br. J. Cancer 84 (2001) 674–679. [PubMed]

[25] Belyakov OV, Folkard M, Mothersill C, Prise KM, Michael BD. A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation. Br. J. Cancer 88 (2003) 767–774. [PubMed]

[26] Shao C, Stewart V, Folkard M, Michael BD, Prise KM. Nitric oxide-mediated signaling in the bystander response of individually targeted glioma cells. Cancer Res. 63 (2003) 8437–8442. [PubMed]

[27] Schettino G, Folkard M, Prise KM, Vojnovic B, Bowey AG, Michael BD. Low-dose hypersensitivity in Chinese hamster V79 cells targeted with counted protons using a charged-particle microbeam. Radiat. Res. 156 (2001) 526–534. [PubMed]

[28] Tartier L, Spenlehauer C, Newman HC, Folkard M, Prise KM, Michael BD, Menissier-de Murcia J, de Murcia G. Local DNA damage by proton microbeam irradiation induces poly(ADP-ribose) synthesis in mammalian cells. Mutagenesis 18 (2003) 411–416. [PubMed]

[29] Nelson JM, Brooks AL, Metting NF, Khan MA, Buschbom RL, Duncan A, Miick R, Braby LA. Clastogenic effects of defined numbers of 3.2 MeV alpha particles on individual CHO-K1 cells. Radiat. Res. 145 (1996) 568–574. [PubMed]