Photodynamic cytotoxicity of mammalian cells exposed to sunlight-simulating near ultraviolet light in the presence of the carcinogen 7, 12-dimethylbenz(a)anthracene

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 enhanced photolethality induced by the sunlight-simulating emission from Westinghouse Sun Lamps (approximately 290-400 nm) but only in the presence of 02. Treatment of cells with DMBA after irradiation was without lethal effect; the endoperoxide of DMBA was ineffective both before as well as after irradiation, and DMBA incubation before far-UV exposure (254 nm) was protective. Cells rendered photosensitive by incubation with DMBA rapidly lost their sensitivity (in < 10 min, 370C) if incubation in a DMBA-free solution containing serum, but maintained their sensitivity at least for several hours if a serum-free solution was used. Although DMBA enhanced light-induced killing of cells in all phases of the cycle, those undergoing DNA syntheses were preferentially sensitized. The data supported 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 single 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. (author)