SIR Medicine Investigation Abstract
CHLOROACETALDEHYDE (CAA) AND THE FORMATION OF ADDUCTS AT THE O6-POSITION OF GUANINE
Presenter:
Xin (Cindy) Wang, Illinois Mathematics and Science Academy, 1500 W. Sullivan Road, Aurora, IL 60506
Mentor:
Dr. Eileen Dolan, University of Chicago
Abstract:
Despite potentially damaging side effects, cyclophosphamide is widely used in cancer cell chemotherapy. Cyclophosphamide forms several metabolites, some of which react with DNA and inhibit further cell replication, resulting in anticancer activity. Unfortunately, unwanted side effects, including bladder carcinogenesis and neurotoxicity, are produced by other metabolites formed from cyclophosphamide, namely chloroacetaldehyde (CAA). This research seeks to determine the structure of the adducts on DNA formed by CAA and whether the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), repairs adducts formed on DNA by CAA. Using high performance liquid chromatography (HPLC), the DNA adducts formed after reaction of CAA with DNA were measured in the presence and absence of AGT. Preliminary results show that AGT alters the concentrations of various adducts found in the CAA-reacted DNA, although the exact composition and identification of the compounds remain unknown.