Strand break induction by photoabsorption in DNA-bound molecules.

Area of Science:

• Biophysics
• Chemical Physics
• Materials Science

Background:

• Platinum complexes are investigated for their potential in cancer therapy.
• Understanding the interaction of platinum compounds with DNA is crucial for developing targeted therapies.
• The Auger effect plays a significant role in radiation-induced DNA damage.

Purpose of the Study:

• To investigate the DNA-damaging potential of a DNA-chloroterpyridine platinum complex.
• To elucidate the role of platinum's L(III) inner-shell excitation in DNA strand breaks.
• To quantify the induction of single-strand breaks (SSBs) and double-strand breaks (DSBs) by Auger processes.

Main Methods:

• Irradiation of dried DNA-platinum complex samples with monochromatic X rays.
• Tuning X-ray wavelengths to the platinum L(III) photoabsorption resonance (on-peak) and below it (off-peak).
• Quantification of SSBs and DSBs by analyzing the conversion of supercoiled DNA plasmids to nicked and linear forms.

Main Results:

• The quantum yield for SSBs was approximately 11, and for DSBs, it was approximately 1.
• On-resonance irradiation significantly increased the production of SSBs and DSBs compared to off-resonance irradiation.
• A 20% increase in the double-strand break to single-strand break ratio was observed upon switching to on-resonance irradiation.

Conclusions:

• Platinum L(III) inner-shell excitation via resonance X-ray irradiation is an effective mechanism for inducing DNA strand breaks.
• The Auger effect following L(III) excitation preferentially contributes to DNA damage, with a notable increase in DSBs relative to SSBs under resonance conditions.
• These findings suggest potential for targeted DNA damage induction in biological systems using specific X-ray energies and platinum complexes.