Induction of mutations by 5-fluorodeoxyuridine: a mechanism of self-potentiated drug resistance?

In medium containing concentrations of deoxycytidine that occur in vivo, 5-fluorodeoxyuridine induced mutation frequencies 6-90 fold greater than spontaneous mutant frequencies at two genetic loci in Chinese hamster cells. In medium lacking deoxycytidine, 5-fluorodeoxyuridine was more cytotoxic but induced no mutants. Hence, the effectiveness of cancer therapy with 5-fluorodeoxyuridine may be limited by self potentiated development of 5-fluorodeoxyuridine-resistant mutants and enhanced and prolonged by manipulating deoxycytidine metabolism.