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Thymidylate Synthase and Dihydropyrimidine Dehydrogenase Levels Are Associated with Response to 5-Fluorouracil in Caenorhabditis elegans  

Kim, Seongseop (Cancer Experimental Resources Branch, National Cancer Center)
Park, Dae-Hun (Cancer Experimental Resources Branch, National Cancer Center)
Shim, Jaegal (Cancer Experimental Resources Branch, National Cancer Center)
Publication Information
Molecules and Cells / v.26, no.4, 2008 , pp. 344-349 More about this Journal
Abstract
5-Fluorouracil (5-FU), a pyrimidine antagonist, has a long history in cancer treatment. The targeted pyrimidine biosynthesis pathway includes dihydropyrimidine dehydrogenase (DPD), which converts 5-FU to an inactive metabolite, and thymidylate synthase (TS), which is a major target of 5-FU. Using Caenorhabditis elegans as a model system to study the functional and resistance mechanisms of anti-cancer drugs, we examined these two genes in order to determine the extent of molecular conservation between C. elegans and humans. Overexpression of the worm DPD and TS homologs (DPYD-1 and Y110A7A.4, respectively) suppressed germ cell death following 5-FU exposure. In addition, DPYD-1 depletion by RNAi resulted in 5-FU sensitivity, while treatment with Y110A7A.4 RNAi and 5-FU resulted in similar patterns of embryonic death. Thus, the pathway of 5-FU function appears to be highly conserved between C. elegans and humans at the molecular level.
Keywords
5-fluorocuracil; C.elegans; dihydropyrimidine dehydrogenase; thymidylate synthase;
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Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 3  (Related Records In Web of Science)
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