Using DNA Devices to Track Anticancer Drug Activity$\backslash $

ORAL

Abstract

h $-abstract-$\backslash $pard It is beneficial to develop systems that represent significant complexity of biological systems, while maintaining control over specific factors involved in a particular process. We have established a chip-based electrochemical platform for following the repair of DNA damage produced by a redox-cycling anticancer drug, beta-lapachone ($\beta $-lap). These chips, which possess key features to reproduce the cellular environment, drug cofactors, and base-excision repair (BER) enzymes tracked DNA damage repair activity with redox probe-modified DNA monolayers on gold. The concentration dependence of {\ss}-lap revealed significant square wave signal changes at levels of high clinical significance as well as sensitivity to sub-lethal levels of {\ss}-lap. We also demonstrate high correlation of this change with the specific drug cycle through rational controls. Thus, this chip-based platform enabled tracking of drug-induced damage repair processes when biological criteria were met, providing a unique synthetic platform for uncovering activity normally confined to inside cells.$\backslash $pard-/abstract-$\backslash $\tex

Authors

  • Dimithree Kahanda

    Department of Physics, The University of Texas at Dallas, 800 W. Campbell Rd., PHY 36, Richardson, TX 75080

  • Jason D. Slinker

    Department of Physics, The University of Texas at Dallas, 800 W. Campbell Rd., PHY 36, Richardson, TX 75080

  • Marc A. Mcwilliams

    Department of Physics, The University of Texas at Dallas, 800 W. Campbell Rd., PHY 36, Richardson, TX 75080

  • Gaurab Chakrabarti

    Departments of Pharmacology, University of Texas Southwestern Medical Center, ND2.210K 601 Forest Park Drive, Dallas, TX 75390-8807

  • David A. Boothman

    Departments of Pharmacology, University of Texas Southwestern Medical Center, ND2.210K 601 Forest Park Drive, Dallas, TX 75390-8807