PHOTODYNAMIC CYTOTOXICITY OF MAMMALIAN CELLS EXPOSED TO SUNLIGHT-SIMULATING NEAR ULTRAVIOLET LIGHT IN THE PRESENCE OF THE CARCINOGEN 7,12-DIMETHYLBENZ(a)ANTHRACENE

Abstract— The coal-derived carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), added to cultures of V79 Chinese hamster, C3H mouse 10T1/ 2 , and human HeLa cells, enhances photolethality induced by the sunlight-simulating emission from Westinghouse Sun Lamps (- 29˜100 nm) but only in the presence of O ₂ . Treatment of cells with DMBA after irradiation is without lethal effect; the endoperoxide of DMBA is ineffective both before as well as after irradiation, and DMBA incubation before far-UV exposure (254 nm) is protective. Cells rendered photosensitive by incubation with DMBA rapidly lose their sensitivity (in < 10 min, 37°C) if incubated in a DMBA-free solution containing serum, but maintain their sensitivity at least for several hours if a serum-free solution is used. Although DMBA enhances light-induced killing of cells in all phases of the cycle, those undergoing DNA syntheses are preferentially sensitized. The data support photodynamic lethality due to one or both of the following: (1) the reaction with DNA of either DMBA radicals followed by oxidation, or DMBA-produced singlet oxygen; or (2) the peroxidation of lysosomal membranes followed by the release of hydrolases including DNAses. As a model system of the combined effects of a fossil-fuel derived polycyclic aromatic hydrocarbon and sunlight, the results with DMBA + near-UV are discussed in the context of altered cell properties (e.g. neoplastic transformation) in sublethally affected cells.