double-strand dna breaks

Irinotecan (CPT-11), a derivative of camptothecin, is an inhibitor of DNA topoisomerase I (Topo I). Irinotecan has antitumor activity by preventing DNA strand reattachment through binding to the Topo I complex, resulting in double-stranded DNA breaks and cell death.

Cylindrospermopsin, a tricyclic uracil derivative, is a cyanobacterial toxin that was first discovered in an algal bloom contaminating a local drinking supply on Palm Island in Queensland, Australia after an outbreak of a mysterious disease. Cylindrospermopsin targets protein and glutathione synthesis in hepatocytes (IC50s = 1.3 and 2.4 µM, respectively), leading to cell death. [1] It has been shown to inhibit the activity of the uridine monophosphate synthase complex with a Ki value of 10 µM.[2] Cylindrospermopsin is genotoxic, inducing DNA damage as evidenced by double strand breaks and reducing cell viability in HepG2 cells at 0.1-0.5 µg ml.[3]