Photosensitized reduction and DNA covalent binding of aziridinylquinones

Abstract

Photolysis of anaerobic aqueous mixtures (at wavelength maxima above 600 nm and at pH 7.4) containing either aluminum phthalocyanine tetrasulfonate (AlPcS 4), chlorin e6 (CHLORIN), pheophorbide-a (PHEO) or a novel tetracationic phthalocyanine derivative (TETCHLORIN) in the presence of the quinones diaziquone (AZQ), carboquone (CARBOQ) or 2,5-dicloro-diaziridinyl-1,4-benzoquinone (AZDClQ) produces the corresponding semiquinones. Photolysis of these mixtures under the conditions stated above, but in the presence of DNA and at pH 5.5 produces quinone–DNA covalent adducts. Absorption bands seen in irradiated solutions suggest binding of these quinones to DNA through the open aziridine ring. In general, the quinone CARBOQ yielded the largest amounts of adducts photosensitized by the dyes studied here. No quinone–DNA adducts were detected if samples were irradiated at pH 7.4.Thus, both photoreduction of these quinones and an acidic environment are needed for these quinones to bind DNA. These results suggest a potential mode of therapy with special applications to hypoxic regions in solid tumors which are characterized by an acidic environment.