@article {Louat553, author = {Thierry Louat and Laurence Servant and Marie-Pierre Rols and Anne Bieth and Justin Teissie and Jean-Sebastien Hoffmann and Christophe Cazaux}, title = {Antitumor Activity of 2',3'-Dideoxycytidine Nucleotide Analog Against Tumors Up-Regulating DNA Polymerase β}, volume = {60}, number = {3}, pages = {553--558}, year = {2001}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {DNA polymerase β (Pol β), an error-prone DNA-synthesizing enzyme tightly down-regulated in healthy somatic cells, has been shown to be overexpressed in many human tumors. In this study, we show that treatment with the 2',3'-dideoxycytidine (ddC) nucleoside analog inhibited in vitro and in vivo the proliferation of Pol β-transfected B16 melanoma cells, which up-regulate Pol β compared with control isogenic cells. The administration of ddC also increased specifically the survival of mice bearing Pol β-overexpressing B16 melanoma. When the phosphorylated form of ddC was electrotransfered into Pol β-transfected melanoma, the cell growth inhibition was strengthened, strongly suggesting that the cytotoxic effect results from incorporation of the chain terminator into DNA. Using in vitro single- and double-stranded DNA synthesis assays, we demonstrated that excess Pol β perturbs the replicative machinery, favors ddC-TP incorporation into DNA, and consequently promotes chain termination. Therefore, the use of chain terminator anticancer agents could be suitable for the treatment of tumors with a high level of Pol β. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/60/3/553}, eprint = {https://molpharm.aspetjournals.org/content/60/3/553.full.pdf}, journal = {Molecular Pharmacology} }