Riboflavin‐mediated cellular photoinhibition of cisplatin‐induced oxidative DNA breakage in mice epidermal keratinocytes

Abstract

Cisplatin is one of the most effective chemotherapeutic agents used in the treatment of various kinds of malignant tumors. A major drawback associated with cisplatin chemotherapy is its cytotoxicity/genotoxicity towards normal tissues. The cytotoxicity has been attributed, in part, to the oxidative stress generated by the drug. Riboflavin is a micronutrient known for its photosensitization characteristics. Owing to the emergence of photodynamic therapy as a modality for the treatment of solid tumors and other accessible lesions in terms of opthalmic, dermatological, cardiovascular and urological diseases, the therapeutic window of riboflavin as a sensitizer has been used to avoid the toxic side effects of cisplatin. Using mice epidermal keratinocytes and comet assay, we show that photochemically activated riboflavin is able to prevent oxidative cellular DNA breakage induced by cisplatin. Irradiation of cells exposed to cisplatin resulted in a dose-dependent increase in the frequency of strand breaks in cellular DNA. Sequential incubation of keratinocytes with riboflavin and cisplatin followed by irradiation led to a significant decrease in strand breakage and reduced the generation of reactive oxygen species. Our results suggest that cisplatin-induced genotoxicity may be blunted or reduced by using riboflavin as a photosensitizer.