alexa Genomic profiling in CEPH cell lines distinguishes between the camptothecins and indenoisoquinolines.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Watson VG, Hardison NE, Harris T, MotsingerReif A, McLeod HL

Abstract Share this page

Abstract We have attempted to use a familial genetics strategy to study mechanisms of topoisomerase 1 (Top1) inhibition. Investigations have steadily been chipping away at the pathways involved in cellular response following Top1 inhibition for more than 20 years. Our system-wide approach, which phenotypes a collection of genotyped human cell lines for sensitivity to compounds and interrogates all genes and molecular pathways simultaneously. Previously, we characterized the in vitro sensitivity of 15 families of Centre d'Etude Polymorphisme Humain (CEPH) cell lines (n = 142) to 9 camptothecin analogues. Linkage analysis revealed a pattern of 7 quantitative trait loci (QTL) shared by all of the camptothecins. To identify which, if any, QTLs are related to the general mechanism of Top1 inhibition or should be considered camptothecin specific, we characterized the in vitro sensitivity of the same panel of CEPH cell lines to the indenisoquinolones, a structurally distinct class of Top1 inhibitors. Four QTLs on chromosomes 1, 5, 11, and 16 were shared by both the camptothecins and the indenoisoquinolines and are considered associated with the general mechanism of Top1 inhibition. The remaining 3 QTLs (chromosomes 6 and 20) are considered specific to camptothecin-induced cytotoxicity. Finally, 8 QTLs were identified, which were unique to the indenoisoquinolines.
This article was published in Mol Cancer Ther and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version