DNA containing incorporated cytarabine residues (Ara-C-DNA)

DNA containing incorporated cytarabine residues represents the primary molecular lesion responsible for the cytotoxic effects of the antimetabolite drug cytarabine (Ara-C). Cytarabine is a pyrimidine analog that is intracellularly phosphorylated to its active form, cytarabine triphosphate (Ara-CTP), which then competes with deoxycytidine triphosphate (dCTP) for incorporation into the DNA strand by DNA polymerases (PubChem CID 6253; StatPearls, "Cytarabine"). Once incorporated, the arabinose sugar moiety creates steric hindrance that inhibits the further progression of DNA polymerase alpha and epsilon, effectively acting as a relative chain terminator (Kufe et al., 1984, PubMed ID 6607275). This incorporation disrupts DNA replication and repair, leading to the formation of double-strand breaks and the activation of apoptotic pathways (Major et al., 1981, PubMed ID 7012535). The extent of cytarabine incorporation into the DNA of leukemic cells is a critical determinant of its therapeutic efficacy, particularly in the treatment of acute myeloid leukemia and other hematologic malignancies (Grant, 1998, PubMed ID 9722531). Because this target is formed during the S-phase of the cell cycle, its formation is highly specific to rapidly proliferating cells, though it also contributes to the drug's significant myelosuppressive side effects. Furthermore, the presence of these residues can interfere with DNA ligation and other enzymatic processes required for genomic stability. Monitoring the levels of Ara-C incorporation serves as a biochemical marker for drug sensitivity in clinical settings.

Other names

Ara-C-incorporated DNACytosine arabinoside-containing DNAArabinosylcytosine-DNADNA-Ara-C

Incorporation into DNA leads to inhibition of DNA polymerase, DNA chain termination, and induction of the DNA damage response.