Low Uracil Concentration in the Liver might be Responsible for the Decreased Antineoplastic Activity of Fluoropyrimidines in Mice with CCl4-Induced Chronic Liver Dysfunction
作者:
Michihiko Tsubono,
Yoshinori Nio,
Shiro Imai,
Takahiro Shiraishi,
Hideki Morimoto,
Chen-Chiu Tseng,
Kazuya Kawabata,
Manabu Fukumoto,
Takayoshi Tobe,
期刊:
Oncology
(Karger Available online 1991)
卷期:
Volume 48,
issue 3
页码: 246-252
ISSN:0030-2414
年代: 1991
DOI:10.1159/000226936
出版商: S. Karger AG
关键词: Fluoropyrimidine;CCl4-induced liver dysfunction;5-Fluorouracil;Tegafur [l-(2-tetrahydrofuryl)-5-fluorouracil];UFT;Carmofur (l-hexylcarbamoyl-5-fiuorouracil)
数据来源: Karger
摘要:
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 CCl4 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 [1-(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.
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