N. Chaudhuri, B. Montag, C. Heidelberger
Apr 1, 1958
Citations
7
Influential Citations
256
Citations
Quality indicators
Journal
Cancer research
Abstract
Summary 1.The excretion, distribution, and metabolism of 5-fluorouracil-2-C 14 and 5-Fluoroorotic-2-C 14 acid have been studied in normal and tumor-bearing mice and in a human cancer patient. 2.Both compounds were rapidly excreted in the urine. 5-Fluorouracil was excreted unchanged shortly after injection. At later times several as yet uncharacterized metabolites were excreted. The radiocarbon appeared much more extentively in the respiratory carbon dioxide following 5-fluorouracil injection than after 5-fluoroorotic acid administration. 3.At all times after intraperitoneal injection of 5-fluorouracil into mice bearing Sarcoma 180, a higher specific activity was found in the tumor than in all other tissues investigated. In the cancer patient the tumor biopsy had a higher specific activity than surrounding skin, muscle, fat, and a liver biopsy. No selective localization of radioactivity in tumor occurred with labeled 5 fluoroorotic acid. 4.5-Fluorouracil and 5-fluoroorotic acid were converted into acid-soluble fluorouridine nucleotides at the mono-, di-, and triphosphate levels, and were incorporated into RNA, but not DNA, in mouse liver, spleen, Sarcoma 180, Ehrlich ascites carcinoma, and a human metastatic carcinoma. The incorporation into RNA at most represented a quantity equivalent to 6 per cent of the uracil content. 5-Fluoroorotic acid was decarboxylated and was present in the RNA as 5-fluorouracil in nucleotide linkage, most probably distributed randomly throughout the macromolecule.