Abstract 1763: A novel synthetic alkylating agent inducing DNA damages is associated with distinct DNA repair pathways

Abstract Alkylating agents are a commonly used category of chemotherapy drugs for a verity type of malignancy. They kill cells by forming DNA adducts and interfering DNA processes if not to being removed. In respect to the types of mono- or bi-functional DNA alkylation, different classes of DNA repair processes are involved. In this study, a new DNA-directed alkylating agent BO738 was investigated. We emphasized to confirming its ability of DNA damage, and revealing which kinds of DNA repair mechanisms to be involved in BO738-induced damage. Our results proved BO738 is a bi-functional alkylating DNA damage agent, evidences including BO738 was able to induce phosphorylation of Chk1, Chk2 and p53, and elevated more potent of FANCD2 monoubiquitination, a hallmark of DNA-crosslink damage, than induced by BCNU. Followed with the finding of DNA damage response, as expected, cells that abolish in removal of BO738-induced DNA damage are link to at least base excision repair, double strand break repair and MGMT-mediate direct repair machineries. In conclusion, we provide a foundation to understand the molecular action of BO738 in subcellular environment, and according that BO738 displays comparable ability in tumor cytotoxicity than BCNU, our study highlighting a therapeutic potential in cancer chemosensitization. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1763. doi:1538-7445.AM2012-1763