Simulation of cell cycle effects on DNA strand break induction due to α-particles

Area of Science:

• Radiation biology
• Cell biology
• Medical physics

Background:

• Radiosensitivity to alpha-particle therapies varies with cell cycle phase.
• Initial DNA strand break yield and repair mechanisms influence radiosensitivity.
• Genome compaction levels change throughout the cell cycle, potentially affecting DNA damage.

Purpose of the Study:

• To simulate the effect of genome compaction changes on DNA strand break induction by alpha-particles.
• To isolate the impact of genome compaction on strand break yield, independent of repair mechanisms.

Main Methods:

• Geant4 simulations were used to model genome compaction metrics (base pair density, chromatin packing, chromosome condensation).
• Simulations included nuclei from G1, S, G2, and M phases of two cancer cell lines and one normal cell line.
• Repair mechanisms were excluded from the simulation to focus solely on compaction effects.

Main Results:

• Varying compaction metrics influenced the strand break yield differently.
• The G2 phase consistently showed the highest strand break yield, while G1 phase showed the least.
• Cancer cell lines exhibited a higher induction of strand breaks compared to the normal cell line.

Conclusions:

• Genome compaction is a key factor influencing the initial yield of radiation-induced DNA strand breaks.
• Cell cycle-dependent changes in genome compaction contribute to radiosensitivity differences among cell lines.
• This simulation provides a foundation for future studies on repair deficiencies and radiation-induced lethality.