Base sequence effects on guanine oxidation by carbonate radical anions: Kinetics and gel electrophoresis studies

TOXI 97

Young Ae Lee, yal1@nyu.edu1, Byeong Hwa Yun, bhy1@nyu.edu1, Seog K Kim, seogkim@yu.ac.kr2, Yelena Margolin, yelya@mit.edu3, Peter C. Dedon, pcdedon@mit.edu4, Nicholas E. Geacintov, nicholas.geacintov@nyu.edu5, and Vladimir Shafirovich, vs5@nyu.edu5. (1) Chemistry, New York University, 29 Washington Place, New York, NY 10003, (2) Chemistry Department, Yeongnam University, 214-1 Dea-dong, Gyongsan, 712-749, South Korea, (3) Biological Engineering Division, NE47-277, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, (4) Division of Bioengineering and Environmental Health, M.I.T, 56-787, Cambridge, MA 02139, (5) Department of Chemistry, New York University, 31 Washington Place, Brown Building, Room 453, New York, NY 10003
Carbonate radicals arise from the decomposition of nitrosoperoxycarbonate, a chemical mediator of inflammation. This radical oxidizes guanine in DNA by electron abstraction reactions that culminates in the formation of guanine oxidation products. However, the mechanisms of action are poorly understood, and the effects of base sequence on the oxidation of the DNA bases have not been characterized. These effects were explored in this work, starting from the kinetics of DNA oxidation, to the formation of chemical products that were detected as alkali-labile lesions. The cascade of events was initiated by utilizing 308 nm XeCl excimer laser pulses to generate carbonate radicals. It has been shown that the base sequence dependence of the initial electron transfer step and the subsequent formation of guanine oxidation products are different from one another. The mechanistic aspects and biological implications of these oxidation reactions in DNA initiated by carbonate radicals will be discussed. Supported by NIH Grant 1 R01 CA110261.
 

General Papers
9:00 AM-11:30 AM, Wednesday, 13 September 2006 Moscone Center -- Room 308, Oral

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Division of Chemical Toxicology

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006