Low uracil concentration in the liver might be responsible for the decreased antineoplastic activity of fluoropyrimidines in mice with ccl4-induced chronic liver dysfunction

Michihiko Tsubono, Yoshinori Νio, Shiro Imai, Takahiro Shiraishi, Hideki Morimoto, Chen Chiu Tseng, Kazuya Kawabata, Manabu Fukumoto, Takayoshi Tobe

Research output: Contribution to journalArticlepeer-review

Abstract

Some fluoropyrimidines are considered to be metabolized in liver microsomes. The present study was designed to assess the effect of chronic liver dysfunction on the antineoplastic activity of fluoropyrimidines. Chronic liver dysfunction was induced in BALB/c mice by 8 weeks of CCU injections. The 5-fluorouracil (5-FU)-sensitive MOPC-104E and 5-FU-resistant Meth-A cells were inoculated subcutaneously into the mice and then various fluoropyrimidines were administered intragastrically. The antitumor activity of the fluoropyrimidines decreased in mice with chronic liver dysfunction, although the concentration of 5-FU in the tumor of normal mice did not differ from that of mice with liver dysfunction. However, the concentration of uracil in the liver was decreased in mice with chronic liver dysfunction. On the other hand, the percent conversion of Tegafur [l-(2-tetrahydrofuryl)-5-FU] to 5-FU in the normal liver did not differ from that in the dysfunctional liver. These results suggest that low uracil concentrations in the liver may result from chronic liver dysfunction and lead to decreased antitumor efficacy of fluoropyrimidines.

Original languageEnglish
Pages (from-to)246-252
Number of pages7
JournalOncology (Switzerland)
Volume48
Issue number3
DOIs
Publication statusPublished - 1991

Keywords

  • 5-Fluorouracil
  • CCU-induced liver dysfunction
  • Carmofur (l-hexylcarbamoyl-5-fluorouracil)
  • Fluoropyrimidines
  • Tegafur [l-(2-tetrahydrofuryl)-5-fluorouracil]
  • UFT

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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