Comparative effects of ftorafur and 5-fluorouracil on DNA synthesis in rat small intestine. |
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Authors: | A M Cohen |
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Institution: | Department of Biopharmaceutical Sciences, College of Pharmacy University of Utah, Salt Lake City, Utah 84112, USA |
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Abstract: | The effect of equimolar doses of ftorafur (100 mg/kg) and 5-fluorouracil (65 mg/kg) on the incorporation of deoxyuridine and thymidine into the DNA of rat small intestine was studied. 5-fluorouracil produced a greater than 90% inhibition of deoxyuridine incorporation within one hour after injection. This degree of inhibition was sustained for at least 12 hours. Deoxyuridine incorporation was inhibited by 30 to 65% during the initial six hours after the injection of ftorafur. By 12 hours the rate of incorporation had returned to 66% of the control value. Neither drug inhibited thymidine incorporation into DNA. A study of the metabolic disposition of radioactively labeled ftorafur and 5-fluorouracil showed that the latter drug was more rapidly and completely converted to fluorouracil-containing nucleotides in the small intestine. The possible relationship between these findings and the reported differences in the toxicity of the two drugs is discussed. |
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