Free radicals-mediated cytotoxicity and genotoxicity of capecitabine in normal and head and neck cancer cells

Capecitabine (Xeloda, CAP), a prodrug of 5-fluorouracil (5-FU), is mainly used in colon cancer, but little is known about its efficacy in head and neck cancer (HNC). In the present work we compared the cyto- and genotoxicity of CAP in HNC HTB-43 cells and human lymphocytes isolated from normal subjects and HNC patients. CAP evoked a decrease in the viability of HNC cells, whereas it did not affect normal lymphocytes. The agent did not interact with isolated plasmid DNA, but it evoked a more pronounced DNA damage in HTB-43 cells than in lymphocytes. CAP induced apoptosis in cancer cells, but not in normal lymphocytes. The drug interfered with cell cycle of the cancer cells. The use of spin traps decreased the DNA-damaging effect of CAP, suggesting that free radicals might be involved in the genotoxic effect of the drug. Capecitabine may evoke a pronounced, free radicals-mediated, cyto- and genotoxic effects in head and neck cancer cells, whereas it may not induce or induce such effects in normal cells to far lesser extent.