UVA-induced oxidation of 6-thioguanine in mammalian cells

TOXI 37

Chunang Gu, cgu001@student.ucr.edu, Environmental Toxicology Graduate Program, University of California at Riverside, Mail Drop 027, Riverside, CA 92521-0403 and Yinsheng Wang, yinsheng.wang@ucr.edu, Department of Chemistry, University of California at Riverside, Mail Drop 027, Riverside, CA 92521-0403.
Azathioprine (Aza), a widely used anti-cancer drug and immunosuppressive agent, could lead to the incorporation of 6-thioguanine (6-TG) into human DNA upon metabolic activation. However, an increased UVA photosensitivity was observed for aza-treated patients. Recently it was found that UVA irradiation of 6-TG-bearing DNA could generate reactive oxygen species, further resulting in mutagenic oxidation products. Here we found that the major UVA photooxidation product of 6-TG is guanine-6-sulfinic acid (Gua-6-SO2H). In addition, Gua-6-SO2H could be converted to guanine-6-sulfonic acid (Gua-6-SO3H) when exposed to air. Interestingly, the rate of this conversion is much slower in oligodeoxyribonucleotides than in mononucleoside. Further studies are being carried out to assess the formation of the two oxidation products of 6-TG in cultured human cells in vivo and to examine the mutagenic properties of Gua-6-SO2H. We believe that the results offer a better understanding of the dramatic increase of skin cancer among patients treated with aza.
 

General Papers: Young Investigator Session
8:00 AM-12:00 PM, Tuesday, 12 September 2006 Moscone Center -- Room 308, Oral

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Chemical Toxicology

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