A new cell culture method for phototoxicity testing: Effects of oral hypoglycemic and diuretic agents

Cervical cells from human in situ carcinoma, the NHIK (Norsk Hydro's Institute for Kreftforskning) 3025 cell, were utilized for screening phototoxic drugs. Sulphonamide oral antidiabetics and diuretics were incubated with the cells for one hour and then irradiated with broad-band UV and UVA. Cell death was dependent on UVA-fluence and drug concentration. Phototoxicity was demonstrated in the presence of two oral antidiabetics and ten diuretics. A number of substances, not previously described to exert phototoxic effects, were detected in this model. Electronmicroscopy showed that biomembranes were the main target, but nuclear damage was also demonstrable. Addition of antioxidants decreased phototoxic cell death, indicating the participation of reactive oxygen species. This model proved not only useful in screening procedures, but also seems suitable for investigating mechanisms of action.