Date of Award
Master of Science
Donald D Ourth
Tryptophan metabolites anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA) have been implicated in the etiology of bladder cancer. Metal-mediated activation of these compounds into mutagens was tested using a plasmid relaxation assay at increasing concentrations of copper (Cu (II) at 5 µM-20 µM in the presence of plasmid pSP-72. One hundred µM 3-OHAA induced plasmid relaxation in the presence of metal cofactor Cu (II) at a concentration as low as 5 µM. The Cu (II) mediated mutagenic activation of 3-OHAA was further investigated using Ames Salmonella/microsome mutagenicity assay with reactive oxygen species (ROS) sensitive tester strain Salmonella TA102. A significant increase in TA102 revertants was observed with an increase in concentration of Cu (II) from 2.5 µg to 50 µg incubated with 100 µg 3-OHAA/plate but not AA. This evidence for mutagenicity with only 3-OHAAin the presence of Cu (II) but not with AA suggests that the presence of the hydroxyl group in 3-OHAAis critical for generating ROSmediated mutagenicity. In summary, this study finds that 3-OHAA, in the presence of the metal cofactor copper causes oxidative stress that damages DNA.
dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.
Gadupudi, Gopi Srinivas, "Evidence for Genotoxicity of 3-Hydroxyanthranilic Acid in the Presence of a Metal Cofactor Copper In Vitro" (2011). Electronic Theses and Dissertations. 279.