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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 O2. 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.