Title

Biological effects of bulky N7- and C8-deoxyguanosine adducts by a site-specific approach

Date of Completion

January 2004

Keywords

Chemistry, Biochemistry

Degree

Ph.D.

Abstract

Compounds that have the ability to alkylate DNA, resulting in the covalent modification of DNA, may induce genetic mutations. Prior studies on the C8-deoxyguanosine (C8-dG) adducts of N-acetyl-2-aminofluorene (AAF), 2-aminofluorene (AF), and 1-aminopyrene (AP), indicate notable similarities in structures, in spite of their different biological effects. However, the biological effects of these adducts have not been compared within the same DNA sequence in cell culture. Also, the major metabolite of the antitumor antibiotic mitomycin C (MC), 2,7-diaminomitosene (2,7-DAM), has the ability to form monoadducts with DNA. In the work described here, comparative mutagenicity of the C8-dG adducts, and the possible mutagenic and cytotoxic effects of the 2,7-DAM-N7-Gua adduct was studied in both bacterial and mammalian cells. ^