Computer evaluation of direct and indirect damage induced by free and DNA-bound iodine-125 in the chromatin fibre.
OBJECTIVE
When Iodine-125 decays within chromatin, several in vivo experiments have shown that the radiobiological effects are caused mainly by indirect mechanisms and that more than one DNA double strand break (DSB) is produced per decay. We present calculations to evaluate the contribution of direct and indirect effects of radiation tracks to produce DNA damage induced by bound and free I-125 in a model of chromatin DNA.


METHODS
A solenoid model of chromatin with 18 nucleosomal elements placed in bulk water (more than 600,000 atoms) is used where the initial I-125 decay takes place. All physical and chemical events initiated by Auger and X-rays were taken into account. The yields of single strand breaks (SSB) and DSB were derived using direct effects on DNA and indirect reactions of all radical species generated in the radiolysis of the bulk water.


RESULTS
The distribution of damage complexity for free and DNA-bound I-125 is presented. We obtained more than 1.3 DSB per decay, with nearly equal contributions from direct and indirect effects. However, for the most complex type of damage, located at the decay site, the direct effect is about 70% of the total number. To show the protective effect of histones, simulations were carried out with and without the presence of histones.
Terrissol
M
M
CPAT, 118 route de Narbonne, F-31062 Toulouse, France. terrissol@cpat.ups-tlse.fr
Edel
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S
Pomplun
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D002843:Chromatin / Q000737:chemistry* / Q000528:radiation effects*; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D018499:Linear Energy Transfer / Q000502:physiology; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D011829:Radiation Dosage
D002843:Chromatin; D007457:Iodine Radioisotopes; D004247:DNA