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Record 1 of 60863
A polymer, random walk model for the size-distribution of large DNA fragments after high linear energy transfer radiation
External Online Source: doi:10.1007/s004119900040
Author and Affiliation:
Ponomarev, A. L.(NASA, Washington DC United States)
Brenner, D.
Hlatky, L. R.
Sachs, R. K.
Abstract: DNA double-strand breaks (DSBs) produced by densely ionizing radiation are not located randomly in the genome: recent data indicate DSB clustering along chromosomes. Stochastic DSB clustering at large scales, from > 100 Mbp down to < 0.01 Mbp, is modeled using computer simulations and analytic equations. A random-walk, coarse-grained polymer model for chromatin is combined with a simple track structure model in Monte Carlo software called DNAbreak and is applied to data on alpha-particle irradiation of V-79 cells. The chromatin model neglects molecular details but systematically incorporates an increase in average spatial separation between two DNA loci as the number of base-pairs between the loci increases. Fragment-size distributions obtained using DNAbreak match data on large fragments about as well as distributions previously obtained with a less mechanistic approach. Dose-response relations, linear at small doses of high linear energy transfer (LET) radiation, are obtained. They are found to be non-linear when the dose becomes so large that there is a significant probability of overlapping or close juxtaposition, along one chromosome, for different DSB clusters from different tracks. The non-linearity is more evident for large fragments than for small. The DNAbreak results furnish an example of the RLC (randomly located clusters) analytic formalism, which generalizes the broken-stick fragment-size distribution of the random-breakage model that is often applied to low-LET data.
Publication Date: Jun 01, 2000
Document ID:
20040131503
(Acquired Oct 19, 2004)
Subject Category: LIFE SCIENCES (GENERAL)
Document Type: Journal Article
Publication Information: Radiation and environmental biophysics (ISSN 0301-634X); Volume 39; 2; 111-20
Publisher Information: Germany
Contract/Grant/Task Num: CA-49062; GM 57245; RR-11623
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: CHROMATIN; DEOXYRIBONUCLEIC ACID; FRAGMENTS; LINEAR ENERGY TRANSFER (LET); MATHEMATICAL MODELS; RANDOM WALK; SIZE DISTRIBUTION; CLUSTER ANALYSIS; COMPUTER PROGRAMS; CULTURED CELLS; DAMAGE; MONTE CARLO METHOD; RADIATION DOSAGE; RADIATION EFFECTS; TELOMERES
Other Descriptors: CHROMATIN/RADIATION EFFECTS; DNA/RADIATION EFFECTS; MODELS, STATISTICAL; ANIMALS; CELL LINE; CLUSTER ANALYSIS; DNA DAMAGE; DOSE-RESPONSE RELATIONSHIP, RADIATION; LINEAR ENERGY TRANSFER; MONTE CARLO METHOD; SOFTWARE; SUPPORT, U.S. GOV'T, NON-P.H.S; SUPPORT, U.S. GOV'T, P.H.S; TELOMERE/RADIATION EFFECTS
Availability Source: Other Sources
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