Studies on fluorinated pyrimidines. VIII. Further biochemical and metabolic investigations.

نویسندگان

  • E HARBERS
  • N K CHAUDHURI
  • C HEIDELBERGER
چکیده

We have previously reported on the tumor inhibitory properties of 5-fluorouracil and 5-fluoroorotic acid (3, 4), prepared by Duschinsky et al. (5), and on the initial clinical trials of 5fluorouracil with patients with far advanced solid tumors (6). The metabolism of 5-fluorouracil and 5-fluororotic acid has been studied, data on excretion and tissue distribution in mice and man have been reported, and the conversion of these compounds into acid-soluble nucleotides and their incorporation into ribonucleic acid have been described (7). Two nucleosides, 5fluorouridine and 5-fluoro-2’-deoxyuridine have been synthesized (8), and their effects on various transplanted tumors have been described (9). The effects of these fluorinated pyrimidines on nucleic acid biosynthesis have been studied in viva (10) and in vitro (ll), where it was shown that they inhibit the methylation of deoxyuridylic acid to thymidylic acid and inhibit the incorporatidn of uracil and erotic acid into RNA. The latter findings have been confirmed by Eidinoff et al. (12) and the conversion of F-uracill into F-uridine and F-UMP has been confirmed by Skiild (13). We have also studied the initial steps in the catabolism of these compounds (2). The present paper describes excretion and metabolic studies with F-uridine and F-duridine and further work on the effects of the series of compounds on nucleic acid biosynthesis in suspensions of Ehrlich ascites cells in a new medium (14). A scheme summarizing all the known biochemical effects of fluorinated pyrimidines will be presented.

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Studies on Fluorinated Pyrimidines

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عنوان ژورنال:
  • The Journal of biological chemistry

دوره 234 5  شماره 

صفحات  -

تاریخ انتشار 1959