We found that i) Itu metabolite could be incorporated into DNA and cause DNA lesions, evidenced by formation of γH2AX and TopBP1 positive nuclear foci and chromosomal breakage; ii) Itu activates Atm, evidenced by S1981 phosphorylation on Atm detected by nuclear foci formation and western blot, and phosphorylation of Chk2; iii) Itu activates p53, evidenced by p53 up-regulation and S15 phosphorylation; iv) Itu causes p53-dependent cell cycle arrest and cell death; v) Itu inhibits tumor growth in carcinoma xenograft mouse models in a p53-dependent manner at low doses. Here, TOPBP1 is linked to neoplasm.