Photosensitized DNA breaks and DNA-to-protein crosslinks induced in human cells by antitumor agent gilvocarcin V

Abstract

The antitumor agent gilvocarcin V (GV) is photoactivated to a genotoxic form by low fluences of near-ultraviolet radiation. Activation of GV by monochromatic 450-nm radiation causes two specific DNA changes in human P3 cells in culture as shown by alkaline elution techniques: single-strand breaks (i.e., alkali-labile sites plus frank strand scissions) and DNA-to-protein covalent bond crosslinks. When GV is present with the cells during irradiation, the yields of these damages are increased. Fluence and concentration studies show that the induction of both DNA lesions occurs at unusually low concentrations of drug and fluences of radiation. Both breaks and crosslinks are readily detectable after exposure to less than 100 kJ m −2 of 405 nm-radiation at a GV concentration of 7.5 × 10 −9 M. These results indicate a possible potential for use of GV in human tumor photochemotherapy.