Inability of Chemically Generated Singlet Oxygen to Break the DNA Backbone

Abstract

The capacity of a photodynamic and a chemical source of singlet molecular oxygen to cause DNA strand breakage at pH 7.8 was compared in the following systems: (1) dissolved rose bengal plus light (400–660 nm), (2) a novel water-soluble naphthalene-derived endoperoxide showing temperature-dependent singlet oxygen release, in the absence of light. Covalently closed circular DNA was efficiently converted to the open (relaxed) form upon exposure to dissolved rose bengal plus light in a time-dependent reaction, showing that this system was capable of causing DNA strand breakage at pH 7.8. The reaction was greatly reduced under hypoxic conditions (< 5 p.p.m. O₂), was stimulated when using D₂O instead of H₂O as a solvent and was not inhibitable by superoxide dismutase, indicating that singlet oxygen was a critical intermediate. However, comparatively large fluxes of singlet oxygen generated by the endoperoxide completely failed to produce DNA strand breaks. We conclude that, although singlet oxygen seems to play a role in DNA strand breakage by rose bengal plus light, singlet oxygen per se is very inefficient if not completely incapable of causing DNA strand breakage.

Key Words:

• DNA strand breakage
• oxidative DNA damage
• photosensitization
• rose bengal
• singlet oxygen