Abstract
The effect of treatment with 5-Fluorouracil (5-FU), a commonly used cytotoxic drug, on the thiamin status of patients with cancer and on that of normal female rats was investigated. Treatment with 5-FU in patients and in the rats resulted in biochemical evidence of thiamin deficiency. This effect was also reflected in depletion of the vitamin content of liver and spleen in the animals. The deficiency, in the patients, studied longitudinally, was rectified by giving a large dose of thiamin (100mg/day) daily for a month. The subjective feeling of well-being was also improved in these patients. Moreover, an increased plasma and urinary ribonuclease (RNase) and urinary hydroxvproline levels were returned to those of the controls by the vitamin administration. In the animals, the whole blood TPP effect and the vitamin store of tissues were not affected when 5-FU was given together with thiamin. The treatment of rats with a high dose of 5-FU resulted in impaired glucose tolerance and in elevated blood levels of pyruvate and lactate. This impairement was also rectified by giving either a high dose of thiamin or thiamin pyrophosphate. The restoration was more marked in the animals given thiamin pyrophosphate. Treatment with 5-FU in the presence of thiamin did not impair the effect of the drug on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and protein content of the liver, spleen and kidney whereas thiamin pyrophosphate appeared to reduce the cytotoxic effect of the drug on liver DNA. This reduction could be due to the protection of normal tissue by thiamin pyrophosphate.