The protective effect of pyrimidine nucleosides on human HaCaT keratinocytes treated with 5-FU.

Therapy with 5-fluorouracil (5-FU) and capecitabine is often complicated by skin toxicity (hand-foot syndrome, HFS). Topical application of uridine ointment is beneficial for alleviating HFS and other pyrimidine nucleosides have been described as 5-FU toxicity modulators. We tested pyrimidine nucleosides and their combinations to find the best combination for topical therapy of HFS. Cellular viability was measured by the real-time cell analyser and methyl thiazol tetrazolium (MTT) assay in order to evaluate the effect of pyrimidine nucleosides on HaCaT keratinocytes treated with 5-FU. The results were confirmed by evaluation of the cellular colonization by microphotography. Cytidine and uridine protected keratinocytes to the same extent. Thymidine enhanced the protective effect when added to cytidine or uridine. Deoxycytidine did not have any protective effect. Our findings support the rationale for using uridine or cytidine in combination with thymidine in ointment for HFS treatment.