MECHANISM OF ACTION AND SPECTRUM OF CELL-TYPES SUSCEPTIBLE TO DOXORUBICIN PHOTOCHEMOTHERAPY

We have shown that, whereas argon ion laser irradiation alone is not c ytocidal for L929 cells, it greatly increases the cytotoxicity of intr acellular doxorubicin. The present study showed that light enhancement of doxorubicin cytotoxicity was not restricted to stock L929 cells, b ut could also be demonstrated using L929 cells selected for doxorubici n resistance and several standard cell lines that are relatively resis tant to doxorubicin prior to selection. Light-enhanced cytotoxicity re sulted in extensive nuclear DNA loss and was strongly inhibited by ano xia. These findings suggest that the mechanism by which light exposure enhances doxorubicin cytotoxicity involves DNA damage by intranuclear generation of reactive oxygen species.