In vitro selection for K562 cells with higher retrovirally mediated copy number of aldehyde dehydrogenase class-1 and higher resistance to 4-hydroperoxycyclophosphamide

Human Gene Therapy
Jan S MorebR Zori

Abstract

Previously, we have reported the successful expression of human aldehyde dehydrogenase class-1 (ALDH-1) in K562 leukemia cells using a retroviral vector and demonstrated low expression that resulted in up to three-fold increase in resistance to 4-hydroperoxycyclophosphamide (4-HC), an active derivative to cyclophosphamide. The purpose of this study was to investigate whether in vitro treatment with 4-HC will allow selection of K562 cells expressing higher levels of ALDH-1, and whether these selected cells are more resistant to 4-HC. Stably transfected or transduced K562 cells with retroviral pLXSN vector containing ALDH-1 cDNA (ALDH-1 cells) were treated repeatedly with 4-HC and then allowed to grow to confluence in liquid culture. Subsequently, the resistance to 4-HC of ALDH-1 cells treated once (ALDH-1+) or twice (ALDH-1++) with 4-HC was compared to ALDH-1 cells or wild-type K562 cells (WT cells). The results show significant increase in 4-HC resistance of ALDH-1+ (2- to 16-fold, p < 0.005) over ALDH-1 or WT cells. No difference was detected between ALDH-1+ and ALDH-1++. In addition, higher ALDH-1 mRNA and enzyme activity were found in ALDH-1+ compared to ALDH-1 cells. Southern analysis of DNA extracted from the different exp...Continue Reading

References

Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J L Ch'ngE W Holmes
May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·D PinkelJ W Gray
Oct 30, 1971·Lancet·M Seabright
Jan 1, 1996·Journal of Synchrotron Radiation·M R PetersonJ R Helliwell

❮ Previous
Next ❯

Citations

Apr 18, 2000·Mutation Research·R B Roth, L D Samson
Nov 15, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Thaer KhouryXinhui Wang
Jan 6, 2006·Drug Metabolism Reviews·Jing ZhangYi-Zhun Zhu
Jun 1, 2013·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Radosław JanuchowskiMaciej Zabel
Dec 1, 2012·Free Radical Biology & Medicine·Surendra SinghVasilis Vasiliou
Oct 28, 2008·Chemico-biological Interactions·Deniz UcarJan S Moreb
Sep 18, 2010·The Journal of Pathology·Malcolm R AlisonLinda J Nicholson
Jun 17, 2000·Biochemical Pharmacology·F GiorgianniR L Blakley
Sep 13, 2005·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jing ZhangShufeng Zhou
Oct 12, 2016·BMC Cancer·Marjorie FlahautAnnick Mühlethaler-Mottet
Sep 28, 2016·International Journal of Cancer. Journal International Du Cancer·Gustav van NiekerkAnna-Mart Engelbrecht
Oct 8, 2004·The Journal of Pharmacology and Experimental Therapeutics·Jan S MorebDagmara Mohuczy
Mar 9, 2018·BioMed Research International·Xiangchou YangHong Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Related Papers

Primary Care Companion to the Journal of Clinical Psychiatry
Hasan MirsalMansur Beyazyürek
Lung Cancer : Journal of the International Association for the Study of Lung Cancer
R Feld
© 2022 Meta ULC. All rights reserved