著者
吉田 光二 星 昭夫 榑谷 和男 金井 貞 市野 元信
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.66, no.5, pp.561-564, 1975-10-31 (Released:2008-10-23)
参考文献数
12

Effect of substitution of 5-position of cyclocytidine with fluorine on its antitumor activity in cultured cells was examined. 5-Fluorocyclocytidine was active against cultured L-5178Y cells similar to cyclocytidine. IC50 of the compound was 0.054μg/ml. This compound inhibited thymidine incorporation into acid-insoluble fraction of the cells. Cell growth inhibition by 5-fluorocyclocytidine was reversed by deoxycytidine but not by thymidine and deoxyuridine. On the other hand, cell growth inhibition by 5-fluorouracil was reversed by thymidine and deoxyuridine. As a result, site of action of 5-fluorocyclocytidine was considered to be similar to that of cyclocytidine and not to 5-fluorouracil.
著者
吉田 光二 星 昭夫 / 実吉 峯郎 MINEO SANEYOSHI
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.30, no.3, pp.1018-1023, 1982-03-25 (Released:2008-03-31)
参考文献数
23
被引用文献数
4 5

The mode of antiproliferative action of two 5-fluorocytosine nucleosides, 5-fluoro-cytidine (FCR) and 5-fluoro-2'-deoxycytidine (FCdR), was examined using mouse leukemia L5178Y cells in vitro. FCR and FCdR were markedly active against L5178Y cells, though the cells were deficient in cytidine deaminase activity. Both compounds increased the incorporation of 14C-labeled thymidine into the acid-insoluble fraction of L5178Y cells and decreased labeled deoxycytidine incorporation. In reversal studies, the antiproliferative effects of both compounds were almost abolished by simultaneous addition of thymidine or deoxyuridine. Deoxycytidine completely reversed the growth inhibition caused by FCdR, but not that caused by FCR. These results demonstrate that the cytotoxicity of both compounds is due to inhibition of thymidylate synthetase, presumably through formation of 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) after deamination by deoxycytidylate deaminase in the pyrimidine de novo pathway.
著者
吉田 光二 榑谷 和男 星 昭夫
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.26, no.2, pp.429-434, 1978-02-25 (Released:2008-03-31)
被引用文献数
2

5-Fluorouridine and 1-β-D-arabinofuranosylcytosine are active against various tumors as antimetabolites. Antitumor activity and mode of action of their nucleotides, 5-fluorouridine 5'-phosphate and 1-β-D-arabinofuranosylcytosine 5'-phosphate, were examined. 5-Fluorouridine 5'-phosphate was active similar to the nucleoside against L1210 leukemia, but the nucleotide showed higher therapeutic ratio than 5-fluorouracil and 5-fluorouridine. The mode of action of these nucleotides was examined by the incorporation of labeled precursors into acid-insoluble fraction of the cells for 30 min. Inhibition patterns of these nucleotides were the same as those of the nucleosides, but the potency of the nucleotides was very weak, and increased with time. Analysis showed that these nucleotides were dephosphorylated on the cell surface and the dephosphorylation was greater than that of phenolphthalein monophosphate. 5-Fluorouridine 5'-phosphate was considered to be a good candidate for an antitumor agent.