title: Using DNA devices to track anticancer drug activity.
abstract: It is beneficial to develop systems that reproduce complex reactions of biological systems while maintaining control over specific factors involved in such processes. We demonstrated a DNA device for following the repair of DNA damage produced by a redox-cycling anticancer drug, beta-lapachone (β-lap). These chips supported ß-lap-induced biological redox cycle and tracked subsequent DNA damage repair activity with redox-modified DNA monolayers on gold. We observed drug-specific changes in square wave voltammetry from these chips at therapeutic ß-lap concentrations of high statistical significance over drug-free control. We also demonstrated a high correlation of this change with the specific ß-lap-induced redox cycle using rational controls. The concentration dependence of ß-lap revealed significant signal changes at levels of high clinical significance as well as sensitivity to sub-lethal levels of ß-lap. Catalase, an enzyme decomposing peroxide, was found to suppress DNA damage at a NQO1/catalase ratio found in healthy cells, but was clearly overcome at a higher NQO1/catalase ratio consistent with cancer cells. We found that it was necessary to reproduce key features of the cellular environment to observe this activity. Thus, this chip-based platform enabled tracking of ß-lap-induced DNA damage repair when biological criteria were met, providing a unique synthetic platform for uncovering activity normally confined to inside cells.
authors.affiliation: Department of Physics, The University of Texas at Dallas, 800 W. Campbell Rd., PHY 36, Richardson, TX 75080, United States.
authors.forename: Dimithree
authors.initials: D
authors.lastname: Kahanda
authors.affiliation: Departments of Pharmacology, Oncology and Radiation Oncology, Laboratory of Molecular Stress Responses and the Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, ND2.210K 601 Forest Park Drive, Dallas, TX 75390-8807, United States.
authors.forename: Gaurab
authors.initials: G
authors.lastname: Chakrabarti
authors.affiliation: Department of Physics, The University of Texas at Dallas, 800 W. Campbell Rd., PHY 36, Richardson, TX 75080, United States.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Mcwilliams
authors.affiliation: Departments of Pharmacology, Oncology and Radiation Oncology, Laboratory of Molecular Stress Responses and the Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, ND2.210K 601 Forest Park Drive, Dallas, TX 75390-8807, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Boothman
authors.affiliation: Department of Physics, The University of Texas at Dallas, 800 W. Campbell Rd., PHY 36, Richardson, TX 75080, United States. Electronic address: slinker@utdallas.edu.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Slinker
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015374:Biosensing Techniques; D002374:Catalase / Q000737:chemistry; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D006046:Gold / Q000737:chemistry; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry; D009285:Naphthoquinones / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; C014638:beta-lapachone; D006046:Gold; D002374:Catalase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
keywords: Base-excision repair; Biosensor; DNA repair; Electrochemical sensor; Oxidative damage