Fast Monte Carlo simulation of DNA damage formed by electrons and light ions

Abstract

The passage of ionizing radiation through living organisms initiates physical and chemical processes that create clusters of damaged nucleotides within one or two turns of the DNA. These clusters are widely considered an important initiating event for the induction of other biological endpoints, including cell killing and neoplastic transformation. Monte Carlo simulations of the DNA damage formation process are a useful adjunct to experiments because they provide additional information about the spatial configuration of damage within a cluster. In this paper, the fast Monte Carlo damage simulation (MCDS) algorithm is re-parameterized so that yields of double-strand breaks, single-strand breaks and sites of multiple base damage can be simulated for electrons, protons and alpha particles with kinetic energies on the order of GeV. The MCDS algorithm provides a useful, quasi-phenomenological scheme to interpolate damage yields from computationally expensive, but more detailed, track-structure simulations. The predicted characteristics of various classes of damage produced by electrons, protons and alpha particles, such as average number of lesions per DNA damage cluster and cluster length in base pairs, are presented. A study examining the effects on damage complexity of an extrinsic free radical scavenger, dimethyl sulfoxide, is also presented. The reported studies provide new information that will aid efforts to characterize the relative biological effectiveness of high-energy protons and other light ions, which are sometimes used in particle therapy for the treatment of cancer.

Microdosimetric relative biological effectiveness of therapeutic proton beams

“…[14] r DSB (y) is derived using the MC Damage Simulation (MCDS) code for proton beams with different energies. [15] It is seen that both weighting functions fall in the region between upper …”

In silico comparasion of 11 different radioisotopes for palliative treatment of bone metastases

“…The studies by Semenenko and Stewart have demonstrated that the results obtained by this simulator correlate well with in vitro results obtained using cell cultures [22]. A detailed description of the MCER algorithm, as well as additional discussions on the validity and limitations of the model can be found in [17] and [21].…”

“…The Monte Carlo excision repair (MCER) algorithm can be used to calculate the formation and repair of DNA damages and to predict repair outcomes such as correct repair, repair with a mutation and conversion into a DSB [21]. The MCER algorithm starts by using the MCDS algorithm to generate a random number of damage configurations expected within the DNA of one cell.…”

“…Another enzymatically distinct repair pathway is nucleotide excision repair (NER). The NER, observed in eukaryotic cells, substitutes oligonucleotide fragments of 24-32 nucleotides in length [21]. Results from this simulator are outputted as simplified repair scenarios, due to the current uncertainties associated with the processing of radiation-induced damage by the BER and NER pathways.…”

“…The cell cycle kinetics can influence and/or be influenced by the kinetics of damage processing; and damages to the DNA are often a trigger for apoptosis, although cell membrane damages can also induce apoptosis [21], [23]. Radiobiological models have been developed to describe the dose-response association, the process of damage production and the key repair mechanisms.…”