DATE: 09-MAR-2006 AUTHOR OF THE MCER 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 MCEER program and related software, please contact Professor Rob Stewart (trebor@purdue.edu). See also http://rh.healthsciences.purdue.edu/ ABOUT THIS FILE This readme file provides a description of software to simulate formation and repair of DNA damage other than double-strand breaks (DSBs) in an average mammalian cell after exposure to ionizing radiation. The program implements a Monte Carlo damage simulation (MCDS) algorithm [1,2] and a Monte Carlo excision repair (MCER) model [3,4]. The combined MCDS/MCER simulations produce estimates of the following quantities: (1) yield of initial DNA damage, such as simple and complex DSBs, single-strand breaks(SSBs), and sites of base damage, (2) probability of excision repair outcomes, i.e., correct repair, repair with a mutation, and formation of a DSB, and (3) number of excision repair cycles needed to remove a DNA damage cluster. HOW TO EXECUTE THE MCER PROGRAM The MCER program can be executed from the MS Windows command prompt or by double clicking on the MCER 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 MCER program from the command prompt, type MCER201 {name of input file} and then press enter. A sample input file (mcer.inp) is provided in the same folder as the MCER executable (MCER201.exe). To execute this program with the mcer.inp file, type MCER201 mcer.inp The program will automatically generate an output file called mcer.out. Both the mcer.inp and mcer.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 MCER 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) | | MCER PARAMETERS | | 8 inhibition distance, Ninh (bp) | | 0.5 probability of choosing a lesion from the first strand, P1 | | 1.0E-4 polymerase error rate for SP BER, etaSP | | 1.0E-6 polymerase error rate for LP BER and NER, etaLP and etaNER | | 0.75 probability of incorrect insertion opposite Bd, phiBd | | 0.75 probability of incorrect insertion opposite Bl, phiBl | |_______________________________________________________________________________| 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. MCER PARAMETERS. Refer to [3] for a detailed description of the MCER model parameters that appear in the input file for the program. A sample header of an output file corresponding to the above input file is shown below. _______________________________________________________________________________ | =============================== | | MCER Version 2.01 19-JAN-2006 | | =============================== | | 0.351 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) | | | | EXCISION REPAIR: | | 8 inhibition distance, Ninh (bp) | | 0.50 probability of choosing a lesion from the first strand, P1 | | 1.0E-04 polymerase error rate for SP BER, etaSP | | 1.0E-06 polymerase error rate for LP BER and NER, etaLP and etaNER | | 0.75 probability of incorrect insertion opposite Bd, phiBd | | 0.75 probability of incorrect insertion opposite Bl, phiBl | |_______________________________________________________________________________| 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; - copy of input parameters used in the simulation of excision repair. Output information provided by the MCDS portion of the 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). Output information provided by the MCER portion of the program includes: - probabilities of three outcomes of excision repair (correct repair, repair with a mutation, and formation of a DSB); - number of repair cycles needed to remove a cluster; - all excision repair data are tabulated for four scenarios: SPBER - all damage is removed by short-patch BER, LPBER - all damage is removed by long-patch BER, NER/SPBER - all base damages are removed by NER and all strand breaks are removed by short-patch BER, and NER/LPBER - all base damages are removed by NER and all strand breaks are removed by long-patch BER. REFERENCES: 1. V.A. Semenenko and R.D. 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 R.D. Stewart, Fast Monte Carlo simulation of DNA damage formed by electrons and light ions. Phys. Med. Biol. 51, 1693-1706 (2006). 3. V.A. Semenenko, R.D. Stewart and E.J. Ackerman, Monte Carlo simulation of base and nucleotide excision repair of clustered DNA damage sites. I. Model properties and predicted trends. Radiat. Res. 164, 180-193 (2005). 4. V.A. Semenenko and R.D. Stewart, 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, 194-201 (2005). ACKNOWLEDGEMENTS AND DISCLAIMER This material was produced with Government support under Grant Numbers DE-FG02-03ER63541 and DE-FG02-03ER63665 (R.D. 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. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof, or Purdue University. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof.