- 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
- 平山 八彦 杉原 太助 浜田 福三郎 金井 貞 疋田 重太郎 荒木 靖雄 博谷 和男 星 昭夫
- 出版者
- The Japanese Cancer Association
- 雑誌
- GANN Japanese Journal of Cancer Research (ISSN:0016450X)
- 巻号頁・発行日
- vol.65, no.2, pp.153-161, 1974-04-30 (Released:2008-10-23)
- 参考文献数
- 23
The distribution in tissues and excretion of cyclocytidine (2, 2'-anhydro-1-β-D-arabinofuranosylcytosine hydrochloride) and its metabolites in urine and feces of macaca monkeys (Macaca irus, Macaca fuscata, and Macaca mulata) and in beagle dogs were examined by the spectrophotometric assay. Distribution of cyclocytidine in plasma and tissues of rats was also examined.The administered cyclocytidine showed a half-life of 22min in plasma of dogs and monkeys, whereas the half-life of aracytidine (1-β-D-arabinofuranosylcytosine hydrochloride) was 47min in plasma of dogs and less than 5min in plasma of monkeys, because of rapid deamination of the comvound to arauridine (1-β-D-arabinofuranosyluracil) in the latter species. Cyclocytidine exhibited maximum concentration in tissues of rats and monkeys at 20 to 40min after the administration, but its metabolites, aracytidine and arauridine, were not detected in these tissues. Cyclocytidine levels in tissues diminished thereafter but were detected within the next 40 to 80min, Neither cyclocytidine nor its metabolites could be detected in the brain. When cyclocytidine was administered intravenously in dogs and monkeys, 65-85% of it was excreted in urine, almost all as intact cyclocytidine, and small amounts of aracytidine and arauridine were detected. On the other hand, the administered aracytidine was excreted only as arauridine in urine of monkeys, and aracytidine and arauridine in dogs. Cyclocytidine and its metabolites were not detected in feces of both species.It might be suggested that the distribution and elimination rate of cyclocytidine after its intravenous administration is not affected by the presence of cytidine deaminase in plasma and tissues.
- 著者
- 濱田 福三郎 杉原 太助 津山 伸吾 平山 八彦 金井 貞 西村 昌数 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.23, no.3, pp.586-591, 1975-03-25 (Released:2008-03-31)
- 被引用文献数
- 1 1
Newly synthesized 5-3H-cyclocytidine was injected intravenously in rhesus monkeys having a high level of cytidine deaminase which inactivates aracytidine, an antitumor substance analogous to cyclocytidine, in human plasma and tissues. After rapid distribution as intact molecule in the liver, kidney, spleen, and other organs, 46.5% of the administered radioactivity was excreted via the renal pathway within 160min. Metabolite analysis of 5-3H-cyclocytidine in plasma, tissues, and urine of the monkeys revealed that extensive or rapid degradation of cyclocytidine did not occur, and confirmed the resistance of cyclocytidine against the deaminase activity and its stability in biological condition in vivo. Phosphorylated derivatives of cyclocytidine were also detected in the monkey liver after injection.
- 著者
- 金井 貞 小嶋 孝志 丸山 修 市野 元信
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.18, no.12, pp.2569-2571, 1970-12-25 (Released:2008-03-31)
- 被引用文献数
- 10 17