Mechanism of cytotoxicity of 5-fluorouracil: distinction between the irreversible cytotoxic effect of 5-fluorouridine and the reversible cytotoxic effect of 5-fluoro-2'-deoxyuridine on murine lymphoma L5178Y cells in culture.
To determine the relative importance of the DNA and RNA effects in the cytotoxicity of 5-fluorouracil, we determined the effects of brief exposure to 5-fluorouridine and 5-fluoro-2'-deoxyuridine, compared with 5-fluorouracil, on the subsequent growth of murine lymphoma L 5178 Y cells during prolonged incubations following the removal of the drug from the culture medium. 5-Fluoro-2'-deoxyuridine markedly inhibited cell proliferation by continuous exposure. However, its inhibitory effect by exposure even at 1,000 muM for 1 h easily disappeared within 1 week after removal of the drug from the culture medium. This result indicates that the cytotoxic effect of 5-fluoro-2'-deoxyuridine is reversible on cell proliferation. On the other hand, the exposure to 5-fluorouridine, even at the low concentration of 1.5 muM for 1 h, caused a substantial and irreversible inhibition on cell proliferation. The cytotoxic effect of 5-fluorouracil was also an irreversible action similar to that of 5-fluorouridine.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005467:Floxuridine / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000473:pathology*; D051379:Mice; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology
D005467:Floxuridine; C001943:5-fluorouridine; D005472:Fluorouracil; D014529:Uridine