Nucleic acids (RNA and DNA) modified by 5-fluorouracil metabolites (5-FU-modified nucleic acids)

RNA and DNA modified by 5-fluorouracil (5-FU) metabolites represent a critical cytotoxic target in oncology. 5-FU, a pyrimidine analog, is converted intracellularly into active metabolites such as 5-fluorouridine triphosphate (FUTP) and 5-fluoro-2'-deoxyuridine triphosphate (FdUTP) [PubMed: 12778130]. These metabolites are misincorporated into cellular RNA and DNA, respectively, substituting for uracil or thymine. The presence of 5-FU in RNA interferes with the processing of ribosomal RNA, the splicing of pre-messenger RNA, and the accuracy of translation, which severely impairs protein synthesis [StatPearls: NBK532925]. In DNA, the incorporation of 5-FU-derived nucleotides leads to genomic instability, DNA strand breaks, and the induction of apoptotic pathways [PubChem: CID 3385]. This dual impact on nucleic acid integrity and function is a primary mechanism by which 5-FU exerts its anti-tumor effects in various malignancies, including colorectal and breast cancers [NIH: NCI Drug Dictionary]. Understanding these interactions is vital for managing drug efficacy and toxicity, particularly in patients with metabolic deficiencies [PubMed: 25230211].

Other names

5-FU-RNA5-FU-DNAFluorinated RNAFluorinated DNA5-fluorouridine-5'-triphosphate (FUTP) target5-fluoro-2'-deoxyuridine-5'-triphosphate (FdUTP) target

5-Fluorouracil is converted into 5-fluorouridine triphosphate (FUTP) and 5-fluoro-2'-deoxyuridine triphosphate (FdUTP), which are misincorporated into RNA and DNA respectively. Incorporation into RNA disrupts normal RNA processing, splicing, and translation, while incorporation into DNA leads to DNA damage, strand breaks, and the activation of DNA repair pathways, ultimately resulting in cell death [PubMed: 12778130].