Biologic effect of 5-fluoro-2'-deoxyuridine incorporation in L1210 deoxyribonucleic acid.

Recent studies have demonstrated that 5-fluoro-2'-deoxyuridine (FdUrd) misincorporates in eukaryotic DNA. We have extended these findings and studied the relationship between DNA incorporation of FdUrd and cell lethality. This required an approach that would distinguish the DNA and RNA effects of this agent. The specific effect of (FdUrd)DNA formation on L1210 clonogenic survival was, therefore, monitored using deoxyuridine (dUrd) to inhibit the metabolism and subsequent incorporation of FdUrd into RNA. The results demonstrated that misincorporation of FdUrd in DNA resulted in lethal cellular events. These observations suggest a new mechanism of action for this cytotoxic and mutagenic agent.