The effect of 5-fluorouracil and cytarabine on human fibroblasts from Tenon's capsule.
The in vitro cellular inhibitory effects of two pyrimidine antimetabolites, 5-fluorouracil (5-FU) and cytarabine (ara-C), on the attachment and proliferation of human Tenon's capsule fibroblasts after 1, 2, 3, 5, 7, and 10 days of growth were measured with a Coulter counter, a colorimetric method using the endogenous enzyme hexosaminidase, and 3H-thymidine uptake. Neither 5-FU nor ara-C affected cell attachment. The 50% inhibitory dose (ID50) for 5-FU, as measured by the Coulter counter and hexosaminidase assay, was 0.2 and 0.4 micrograms/ml, respectively, at day 5 and decreased to 0.01 and 0.10 micrograms/ml, respectively, on later days. The ID50 for ara-C as measured by the Coulter counter and hexosaminidase assay was 0.01 and 0.1 micrograms/ml at day 3 and remained constant over time. Much lower ID50s were measured by thymidine uptake for both drugs. These findings may indicate that 5-FU has a delayed effect on cellular proliferation due to conversion into more active metabolites. The ara-C has a direct and constant inhibitory effect on cellular proliferation and is ten times more potent than 5-FU as an antiproliferative drug. Thus ara-C may have clinical utility in preventing failure of glaucoma filtering surgery.
Lee
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DA
Jules Stein Eye Institute, University of California 90024-7004.
Shapourifar-Tehrani
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S
Kitada
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S
D000869:Anterior Eye Segment / Q000166:cytology* / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003124:Colorimetry; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D005472:Fluorouracil / Q000494:pharmacology*; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans
D003561:Cytarabine; D004247:DNA; D006596:Hexosaminidases; D005472:Fluorouracil