Particle induced strand breakage in plasmid DNA

PhD ceremony: Ms. H.M. Dang, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Thesis: Particle induced strand breakage in plasmid DNA

Promotor(s): prof. R. Hoekstra

Faculty: Mathematics and Natural Sciences

Ionizing radiation affects our daily life, for example in the form of cosmic rays, environmental radiation or during cancer therapy treatments. Different kinds of radiation behave different when they interact with matter, and in particular with biological cells. Classical radiation therapy for decades relied on the use of energetic photons or electrons for controlled cell-killing. In recent years, alternative treatments based on fast protons or heavy ions have proven their advantage for particular types of tumors. One of the main differences between the various types of radiation is how the particle energy is deposited as a function of depth. Ions have a very special depth distribution of the deposited dose, peaking at the end of the particle's track. At this Bragg peak, the relative biological effectiveness is highest i.e. the damage is maximum.

When ionizing radiation crosses a living cell, direct ionization and fragmentation of biologically relevant molecules such as DNA occurs but also indirect DNA damage due to i.e. OH radicals stemming from water radiolysis. DNA damage can be in the form of single strand breaks, double strand breaks or more complex lesions which are very difficult to repair.

In this thesis, interactions of heavy ions and protons with plasmid DNA were explored for kinetic energies corresponding to extreme regions along the Bragg-curve. Both dry plasmids and plasmids in aqueous solution were studied to investigate the relevance of direct effects. The experimental results indicate that for a given dose, at the Bragg peak DNA damage is qualitatively most severe.