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pubmed:abstractText |
Cytotoxicity from the anticancer drug 2',2'-difluoro-2'-deoxycytidine (dFdCyd) has been correlated with its incorporation into DNA. However, cytotoxicity may also result from inhibition of DNA synthesis, due to either (1) dFdCyd diphosphate-mediated inhibition of ribonucleotide reductase, or (2) direct inhibition of DNA polymerases by the 5'-triphosphate of dFdCyd (dFdCTP). To elucidate the role of DNA synthesis inhibition in the cytotoxicity of dFdCyd, we compared dFdCyd to hydroxyurea (HU), a ribonucleotide reductase inhibitor, and aphidicolin, an inhibitor of DNA polymerases, in the U251 and D54 human glioblastoma cell lines.
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pubmed:affiliation |
Department of Pharmacology, University of Michigan Medical Center, 1310 E Catherine St, Ann Arbor, MI 48109-0504, USA.
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