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International Journal of Radiation Biology 73, 149-156, 1998

Radiation-Induced Total-Deletion Mutations in the Human hprt Gene: A Biophysical Model Based on Random Walk Interphase Chromatin Geometry

Indexing words: Biophysical modeling, mutation, hprt, radiation, chromosome aberration.
ABSTRACT
A biophysical model is developed for the sizes of radiation-induced hprt deletions. Deletions are assumed to be produced by two DSBs that are closer than an interaction distance at the time of DSB induction. Interphase chromatin is modeled by a biphasic random walk distribution. Assuming that the two DSBs are produced from two separate tracks at low-LET, we calculate the size spectra for total deletions of the hprt gene. Comparing with the results of Yamada et al. (Rad. Res. 145, 481-490, 1996) for g-irradiated human fibroblasts we find that an interaction distance of 0.75 micrometers will fit both the absolute frequency and the size spectrum of the total deletions. We also show that high-LET radiations produce, relatively, more total deletions of sizes below 0.5 Mb. It has been suggested that an essential gene is located about 1.36 Mb from the hprt locus towards the telomere. The model predicts another essential gene to be located between 2 and 3 Mb from the hprt locus towards the centromere. Using the same assumptions and parameters as for evaluating mutation frequencies, we also calculate a frequency of intra-arm chromosome deletions that is in agreement with experiments. The calculation suggests that total-deletion mutations of the human hprt gene and intrachange chromosome aberrations share a common mechanism for their induction.

H. Wu*,&, R. K. Sachs# and T. C. Yang*,@ *NASA Johnson Space Center, Radiation Biophysics Laboratory and &Kelsey-Seybold Clinic, Mail Code SD2, Houston Texas 77058, USA; #Department of Mathematics, University of California, Berkeley, California 94720, USA
@Corresponding author Dr. Tracy C. Yang NASA Johnson Space Center Mail Code SD2 Houston, TX 77058 USA Phone: 281-483-5583 Fax: 281-483-3058 e-mail: tyang@sdmail.jsc.nasa.gov
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