6-thio-2′-Deoxyguanosine (6-thio-dG) is a nucleoside analog that is incorporated into de novo-synthesized telomeres by telomerase. This induces telomerase dysfunction resulting in telomeric DNA damage and rapid cell death. This process occurs in cells expressing telomerase but not in telomerase-negative cells. DNA containing 6-thio-dG inhibits the function of RNase H, preventing the cleavage of DNA-RNA heteroduplexes. In mouse xenograft studies using A549 lung cancer cells, 6-thio-dG causes a decrease in tumor growth rate associated with telomere dysfunction.
