Alejandro Bertolet, PhD

Alejandro Bertolet, PhD, of the Mass General Department of Radiation Oncology, was the lead author of a recent study in Radiation Research, Impact of DNA Geometry and Scoring on Monte Carlo Track-Structure Simulations of Initial Radiation-Induced Damage.

What Question Were You Investigating?

Radiation therapy utilizes the capability of ionizing radiation to kill cells in a favorable way, aiming at killing tumor cells while sparing healthy ones.

The main mechanism of action is the damage produced by radiation to the DNA in the cell nucleus, which unchains different mechanisms impairing the cells' ability to repair the damage, reproduce and survive.

Different types of ionizing radiation are capable of producing more complex and densely packed damage, which in turn makes it harder for the cell to repair the induced damage.

In this sense, computational simulations using well-known physics and the Monte Carlo method offer an ideal platform to study the differences in the damage induced to the DNA by different radiation types.

Our study provides a thorough revision of the methods employed to perform these simulations, including the physical damage induced directly by the radiation itself, but also the indirect damage produced at a later stage after radiation breaks water molecules in the surrounding areas.

We also provide results of damage induced by protons and alpha particles of different energies and benchmark our results against basic radiochemistry studies that have been conducted for decades.

We expect this study will help other researchers elucidate the physical and chemical effects of radiation damage.

What Did You Find?

In this work, we used the Monte Carlo track structure tool TOPAS-nBio, built on top of Geant4-DNA, for simulation at the nanometer scale to evaluate differences among three DNA geometrical models in an entire cell nucleus, including a sphere/spheroid model specifically designed for this work.

In addition to strand breaks, we explicitly consider the direct, quasi-direct, and indirect damage induced to DNA base moieties.

We used a new algorithm to characterize the damage to the DNA induced by radiation directly and by free radicals produced after water radiolysis indirectly, providing guidelines to perform this task in MC radiobiology simulations.

Damage to the DNA induced by protons and alpha particles of different energies were simulated and the results or our modeling were consistent with those published in basic radiochemistry and radiobiology experimental studies.

We plan to use our MC simulations to figure out the biological effectiveness of “hard” radiations such as alpha particles, particularly in the context of radiopharmaceutical therapy, which is receiving an increasing level of attention in the cancer care community as a promising targeted approach.

What's Next?

After characterizing damage induced initially by alpha particles, we will include models for damage repair depending on different cell types or cell lines, thus generating a database of RBE for alpha particles for cellular/nuclear effects in tumor and normal tissue cells.  

Paper Cited:

Bertolet, A., Ramos-Méndez, J., McNamara, A., Yoo, D., Ingram, S., Henthorn, N., Warmenhoven, J. W., Faddegon, B., Merchant, M., McMahon, S. J., Paganetti, H., & Schuemann, J. (2022). Impact of DNA Geometry and Scoring on Monte Carlo Track-Structure Simulations of Initial Radiation-Induced Damage. Radiation research, 198(3), 207–220.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.