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IRSN, Institut de radioprotection et de sûreté nucléaire

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Enhancing Nuclear Safety


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Induction and repair rate of DNA damage : a unified model for describing effects of ionizing radiation and heavy metals


Journal title : Journal of Theoretical Biology
Volume : 251
issue: 1
Pagination : 68-81
Publication date : 01/03/2008

Summary

DNA is a key-target for genotoxic stress. Hence, the knowledge of induction and repair rate of DNA damage are very useful to describe and predict toxicity of situations involving stress. Unfortunately, induction and repair rate are generally assessed separately whereas they act either concomitantly or transiently in living organisms, rendering therefore very complex the assessment of both features of response to stress. Furthermore, this problem raises the question whether DNA repair process adapt or not to respond to different amount of DNA damage. In a previous report, we proposed a stochastic interpretation of the repair rate of the major radiation-induced DNA damage. We provided evidence that DNA repair probabilities obey the Gamma distribution (Foray et al., 2005). Here, to better describe situations in which DNA damage induction and repair occur together, our biostatistical model was modified by the introduction of a DNA damage induction parameter. Theoretical and experimental data were compared and discussed by taking concrete experimental situations: X-rays irradiation at different dose-rates and contamination with heavy metal and detection of DNA damage by immunofluorescence. By assuming that DNA repair rate is invariant whatever the amount of DNA damage, our model provides good prediction of experimental data suggesting the relevance of our model. Since a major aim of radiobiologists is to better understand the molecular bases of radiosensitivity, we hope that our model will serve as a quantitative and qualitative evaluation of early stress-induced events that condition the tissular and clinical response to stress.

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