2001 Fiscal Year Final Research Report Summary
A NEW DELIVERY SYSTEM FOR 5-FLUOROURACIL USING PRODRUG AND CONVERTING ENZYME
| Project/Area Number |
12671700
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Shinshu University |
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Principal Investigator |
KOMURASAKI Yusuke Shinshu University Hosital, Department of Ophthalmology, Lecturer, 医学部・附属病院, 講師 (90303479)
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| Co-Investigator(Kenkyū-buntansha) |
KURIMOTO Yasuo Shinshu University, Department of Ophthalmology, Lecturer, 医学部, 講師 (50293519)
SHIBUKI Hiroto Shinshu University, Department of Ophthalmology, Assistant, 医学部, 助手 (70313864)
YOSHIMURA Nagahisa Shinshu University, Department of Ophthalmology, Professor, 医学部, 教授 (70211662)
AKIMOTO Masayuki Shinshu University, Department of Ophthalmology, Assistant, 医学部, 助手 (90303453)
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| Project Period (FY) |
2000 – 2001
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| Keywords | 5-fluorouracil / 5-fluorocytosine / cytosine deaminase / adenoviral vector / gene therapy / filtering surgery / 緑内障 |
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| Research Abstract |
Aims. To evaluate a new delivery system of 5-fluorouracil ( 5-FU ) using 5-fluorocytosine ( 5-FC ) as a prodrug and cytosine deaminase induced in vitro and in vivo.
Methods. Fibroblastic cells from rabbit Tenon's capsule were cultured. The cells were exposed to 5-FU arid 5-FC with or without cytosine deaminase induced by recombinant adenovirus. In vitro study, cell proliferation and DNA synthesis were assessed by MTS, BrdU assay. The effect of 5-FC removal after the treatment of 5-FC and cytosine deaminase induction was also assayed.
In vivo study, cells with or without cytosine deaminase induction were transplanted into subconjunctival space of mice, followed by eye drops of 1,000 μg/ml of 5-FC three times a day. The mice were sacrificed at day1, 5, and 10, then the cells transplanted were evaluated.
Results. Cell proliferation was inhibited by exposure to 5-FU as dose dependent manner, however up to 1 ,000 μg/ml of 5-FC did not affect cell proliferation. Cell proliferation was inhibited by exposure to 5-FC as time dependent manner with induction of cytosine deaminase following infection of recombinant adenovirus. When 5-FC was removed three or six days after the treatment, the cells grew again. The effect was reproduced in vivo model of subconjunctival cellular proliferation although 5-FC was administrated as eye drops. There were no cases having corneal erosion.
Conclusion. In this study we showed cell proliferation was inhibited by co-exposure of 5-FC and cytosine deaminase. This new delivery system may merit in control delivery of 5-FU after filtering surgery.
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Research Products
(2 results)
