Several drugs that are used in the treatment of bacterial infections or in cancer chemotherapy act by inhibiting nucleotide biosynthesis, either directly or indirectly. Antimetabolites used in cancer chemotherapy are toxic to rapidly dividiug cells including those of the bone marrow and intestinal epithelia. Consequently agents that inhibit nucleotide synthesis must be uscd judiciously. Fluorouracil (5-FU) interferes with thymidylate synthesis (Figure 14-13). Inhibition of thymidylate synthase decreases cellular levels of the thymidine nucleotides. Cells lacking thymine are prone to die, a phenomenon called "thymineless death." The mechanism for this response is unclear. Fluorouracil is used in the treatment of a variety of solid tumors including carcinoma of the ovary, cervix, bladder, prostate, and gastrointestinal tract. Mercaptopurine is a potent inhibitor of purine nucleotide biosynthesis. This agent, which is a hypoxanthine analogue, must first be converted to 6-thioinosine 5'-monophosphate (Table 14-3).