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A Forward Genetic Approach for Analyzing the Mechanism of Resistance to the Anti-Cancer Drug, 5-Fluorouracil, Using Caenorhabditis elegans  

Kim, Seongseop (Cancer Experimental Resources Branch, National Cancer Center)
Shim, Jaegal (Cancer Experimental Resources Branch, National Cancer Center)
Publication Information
Molecules and Cells / v.25, no.1, 2008 , pp. 119-123 More about this Journal
Abstract
Pyrimidine antagonists including 5-Fluorouracil (5-FU) have been used in chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a mainstay treatment for colorectal cancer. It is a pro-drug that is converted to the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5-FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One of the major obstacles to successful chemotherapy is the resistance of cancer cells to anti-cancer drugs. Therefore, it is important to elucidate resistance mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a model system to investigate the mechanism of resistance to 5-FU, which induces germ cell death and inhibits larval development in C. elegans. We screened 5-FU resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants out of 72,000 F1 individuals screened, and mapped them into three complementation groups. We propose that C. elegans could be a useful model system for studying mechanisms of resistance to anti-cancer drugs.
Keywords
5-Fluorouracil; Anti-Cancer Drug; C. elegans; Mutant Screen; Resistance;
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Times Cited By KSCI : 3  (Citation Analysis)
Times Cited By Web Of Science : 6  (Related Records In Web of Science)
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