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)
  • Received : 2007.08.27
  • Accepted : 2007.09.13
  • Published : 2008.02.29


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.


5-Fluorouracil;Anti-Cancer Drug;C. elegans;Mutant Screen;Resistance


Supported by : National Cancer Center


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