Electronic Theses and Dissertations

Identifier

364

Date

2011

Document Type

Thesis

Degree Name

Master of Science

Major

Biology

Committee Chair

King-Thom Chung

Committee Member

Donald D Ourth

Committee Member

Carlos Estrano

Abstract

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.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.

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