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