Modelling the effect of incorporated halogenated pyrimidine on radiation-induced DNA strand breaks

Watanabe, Ritsuko; Nikjoo, H.*

Incorporation of halogenated pyrimidines, iodo- and bromo-deoxyuridines (HP), into DNA is known to sensitize cells to radiation. The aim of this study is to estimate the enhancement of DNA strand break induced by low LET radiation in the presence of HP and examine source, complexity and clustering properties of damage that could provide correlation between DNA damage and lethality. Monte Carlo track structure methods were used to model the induction of strand breakage by X-ray photons. As a result, the increase of strand breaks due to Br/IdU incorporation could be explained by the mechanism of uracilyl radical production originated from e-aq and direct hits on bases. The significant contribution of electron migration along DNA within limited distance is shown. It is also shown that the incorporation of Br/IdU causes a spectral shift towards greater complexity of clustered DNA damage. Further, it has been supported that DSB is responsible for radiation-induced cell killing.