DATE: 10-MAR-2006 AUTHOR OF THE MCDS COMPUTER PROGRAM: Vladimir Semenenko, Ph.D. School of Health Sciences Purdue University 550 Stadium Mall Drive West Lafayette, IN 47907-2051 CORRESPONDENCE: For additional information about the MCDS program and related software, please contact Professor Rob Stewart (trawets@uw.edu). See also http://rh.healthsciences.purdue.edu/ ABOUT THIS FILE: This readme file provides a description of software to simulate formation of DNA damage in nuclear DNA after exposure to ionizing radiation. The program implements a Monte Carlo damage simulation (MCDS) algorithm [1] that was re-parameterized [2] so that yields of double- strand breaks, single-strand breaks, and sites of multiple base damage can be simulated for electrons, protons and alpha particles with kinetic energies on the order of GeV. The MCDS simulations also provide information about the characteristics of various classes of DNA damage, such as the average number of lesions per DNA damage cluster and the average cluster length in base pairs. HOW TO EXECUTE THE MCDS PROGRAM: The MCDS program can be executed from the MS Windows command prompt or by double clicking on the MCDS executable. The command prompt can be accessed from the start menu by typing command.com from the run menu-item. Alternatively, the command prompt can (usually) be accessed from the Program Accessories menu item. Refer to your MS Windows documentation for more detailed information on how to access and use the command prompt. To execute the MCDS program from the command prompt, type MCDS201 {name of input file} and then press enter. A sample input file (mcds.inp) is provided in the same folder as the MCDS executable (MCDS201.exe). To execute this program with the mcds.inp file, type MCDS201 mcds.inp The program will automatically generate an output file called mcds.out. Both the mcds.inp and mcds.out files are ASCII text files. It is recommended that you open and edit these files using a program such as the NotePad application that comes with MS Windows. Some additional sample input files can be found in the .\ubeam folder DESCRIPTION OF MCDS INPUT FILES A sample input file for the computer program is shown below. _______________________________________________________________________________ | 1234567890 seed [1, 2147483646]; zero or negative number to randomize | | 1000 number of cells | | MCDS PARAMETERS | | 4He particle (e for electrons, 1H for protons, etc.) | | 5.0 particle energy (MeV) | | 0.0 fraction Bl/Bd | | DMSO SIMULATION PARAMETERS | | 0.5 fraction of non-scavengeable DNA damage | | 0.5 concentration at half-level (mol dm^-3) | | 0.0 DMSO concentration (mol dm^-3) | |_______________________________________________________________________________| A brief description of input parameters: SEED for a random number generator - integer in the range between 1 and 2147483646. If zero or negative value is specified for this parameter, the seed will be determined from a system clock. NUMBER OF CELLS. All data produced by the program are reported as mean values and the corresponding standard errors of the mean. This parameter specifies the number of program runs used for averaging results. PARTICLE. Charged particle symbol: e for electrons, 1H for protons, 4He for alpha particles. PARTICLE ENERGY. Particle energy in MeV. The minimum kinetic energy for which simulations can be performed is 0.00008 MeV for electrons, 0.105 MeV for protons and 2 MeV for alpha particles. FRACTION BL/BD. This parameter specifies the fraction of sites of base loss in the total number of base damages. In the absence of other information the default value of zero should be used for this parameter. DMSO SIMULATION PARAMETERS. Parameters used to simulate the presence of an endogenous free radical scavenger DMSO in the system. For a detailed description see [2]. To perform simulations for a normal cellular environment, set DMSO concentration to zero. If DMSO concentration is set to zero, values of the other two parameters do not have effect on program results. A sample header of an output file corresponding to the above input file is shown below. _______________________________________________________________________________ | =============================== | | MCDS Version 2.01 19-JAN-2006 | | =============================== | | 0.092 running time (min) | | 1234567890 seed | | 1000 number of cells | | | | RADIATION TYPE: 4He | | 5.0000E+00 Kinetic energy (MeV) >= 1.9882E+00 MeV | | 3.7264E+03 Rest mass energy (MeV) | | 5.1751E-02 Speed (beta=v/c) | | 1.4432E+03 (Zeff/beta)^2 <= 3200 | | | | DAMAGE FORMATION AND CLUSTERING: | | 44896 segment length, nseg (bp per cell per Gy) | | 1300 number of strand breaks, sigSb (per cell per Gy) | | 3900 number of base damages, sigBd (per cell per Gy) | | 3.0 base damage to strand break ratio, f | | 9 minimum distance between clusters, Nmin (bp) | | 10 maximum distance between two Sb to compose a DSB, Ndsb (bp) | | 0.0 fraction Bl/Bd | | | | DMSO SIMULATION: | | 5.0000E-01 fraction of non-scavengeable DNA damage | | 5.0000E-01 concentration at half-level (mol dm^-3) | | 0.0000E+00 DMSO concentration (mol dm^-3) | |_______________________________________________________________________________| The header provides the following information: - program execution time in minutes; - seed (either the seed specified by the user in the input file or a value that was determined using the system clock); - number of program runs used to obtain reported mean and standard error values; - radiation type (e, 1H or 4He); - particle kinetic energy in MeV from the input file versus the minimum kinetic energy that can be simulated; - rest mass energy for the particle in MeV; - velocity of the particle relative to the speed of light in vacuum; - ratio (Zeff/beta)^2 for the specified particle and energy versus the maximum (Zeff/beta)^2 value that can be simulated; - damage formation and clustering parameters used by the MCDS algorithm. For a description of these parameters see [1,2]; - copy of input parameters for the DMSO simulation. Output information provided by the MCDS program includes: - percent yields of damage grouped according to a classification scheme of Nikjoo et al. (see Int. J. Radiat. Biol. 71, 467-483, 1997 and Radiat. Res. 156, 577-583, 2001); - yields of different classes of damage (double-strand breaks, single-strand breaks and sites of multiple base damage) per Gy per cell; - composition of clusters, i.e., percentage of strand breaks and damaged bases; - cluster length in base pairs for different classes of damage; - density of strand breaks and base damages within a cluster (number of lesions per unit cluster length). REFERENCES: 1. V.A. Semenenko and http://www.radonc.washington.edu/faculty/stewart/, A fast Monte Carlo algorithm to simulate the spectrum of DNA damages formed by ionizing radiation. Radiat. Res. 161, 451-457 (2004). 2. V.A. Semenenko and http://www.radonc.washington.edu/faculty/stewart/, Fast Monte Carlo simulation of DNA damage formed by electrons and light ions. Phys. Med. Biol. 51, 1693-1706 (2006). ACKNOWLEDGEMENTS AND DISCLAIMER This material was produced with Government support under Grant Numbers DE-FG02-03ER63541 and DE-FG02-03ER63665 (http://www.radonc.washington.edu/faculty/stewart/, Principal Investigator) awarded by the United Department of Energy. Neither the United States Government nor the United States Department of Energy, nor Purdue University, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, software or process disclosed, or represents that its use would not infringe privately owned rights. 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