Radiation-induced total-deletion mutations in the human hprt gene: a biophysical model based on random walk interphase chromatin geometry.
OBJECTIVE
To develop a biophysical model that explains the sizes of radiation-induced hprt deletions.


METHODS
Key assumptions: (1) Deletions are produced by two DSB that are closer than an interaction distance at the time of DSB induction; (2) Interphase chromatin is modelled by a biphasic random walk distribution; and (3) Misrejoining of DSB from two separate tracks dominates at low-LET and misrejoining of DSB from a single track dominates at high-LET.


RESULTS
The size spectra for radiation-induced total deletions of the hprt gene are calculated. Comparing with the results of Yamada and coworkers for gamma-irradiated human fibroblasts the study finds that an interaction distance of 0.75 microm will fit both the absolute frequency and the size spectrum of the total deletions. It is also shown that high-LET radiations produce, relatively, more total deletions of sizes below 0.5 Mb. The model predicts an 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, a frequency of intra-arm chromosome deletions is calculated that is in agreement with experimental data.


CONCLUSIONS
Radiation-induced total-deletion mutations of the human hprt gene and intrachange chromosome aberrations share a common mechanism for their induction.
Wu
H
H
NASA Johnson Space Center, Radiation Biophysics Laboratory, Houston, TX 77058, USA.
Sachs
R K
RK
Yang
T C
TC
D055592:Biophysical Phenomena; D001703:Biophysics; D002478:Cells, Cultured; D002843:Chromatin / Q000648:ultrastructure*; D016386:Chromosome Walking; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D005347:Fibroblasts / Q000528:radiation effects / Q000648:ultrastructure; D017353:Gene Deletion; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007399:Interphase; D018499:Linear Energy Transfer; D008432:Mathematical Computing; D008957:Models, Genetic; D009154:Mutation / Q000528:radiation effects*
D002843:Chromatin; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase