PMID: 8943065Nov 26, 1996Paper

Retroviral transduction of a mutant methylguanine DNA methyltransferase gene into human CD34 cells confers resistance to O6-benzylguanine plus 1,3-bis(2-chloroethyl)-1-nitrosourea

Proceedings of the National Academy of Sciences of the United States of America
Jane S ReeseS L Gerson

Abstract

Human CD34 cells express low levels of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) and are sensitive to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Gene transfer of the AGT gene, methylguanine DNA methyltransferase (MGMT), results in only modest BCNU resistance. Recently, an AGT inhibitor, O6-benzylguanine (BG), entered clinical trials. In preclinical studies, BG potentiated the cytotoxic effect of BCNU in tumors but increased toxicity to normal CD34 cells. We transferred a mutant MGMT containing a glycine-to-alanine mutation at position 156, resulting in marked resistance to BG, into Chinese hamster cells; the K562 cell line and human CD34 cells used the retroviral backbone MFG. In each instance, cells expressed increased AGT and were much more resistant to the combination of BG and BCNU than the parental cells or cells transduced with wild-type MGMT. Furthermore, the transduction efficiency in human CD34 cells was in excess of 70%, and the proportion of CD34 transduced cells resistant to the combination was > 30%. Thus, retroviral-mediated transduction of a mutant MGMT into CD34 cells appears to be an effective way to induce selective resistance to a drug combination designed to overcome a significant r...Continue Reading

References

Mar 3, 1992·Biochemical Pharmacology·S L GersonJ K Willson
May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D M BodineA W Nienhuis
Dec 1, 1985·The Journal of Clinical Investigation·S L GersonN A Berger

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Citations

Mar 11, 2000·Environmental and Molecular Mutagenesis·M Limp-Foster, M R Kelley
Sep 25, 2001·The Journal of Pathology·A M JubbP Quirke
Aug 1, 1997·Molecular Medicine Today·R MazeD A Williams
Apr 18, 2000·Mutation Research·R B Roth, L D Samson
Aug 9, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Rustom FalahatiKarin Ml Gaensler
Aug 22, 2002·Nature Reviews. Cancer·Brian P Sorrentino
Apr 12, 2000·European Journal of Biochemistry·G Frosina
Mar 29, 2001·Journal of Hematotherapy & Stem Cell Research·J S ReeseS L Gerson
Oct 24, 2001·Journal of Hematotherapy & Stem Cell Research·K LeeO N Koç
May 3, 2000·Journal of Hematotherapy & Stem Cell Research·J S ReeseS L Gerson
Jun 17, 2010·The Journal of Clinical Investigation·Brian C BeardHans-Peter Kiem
Nov 5, 2005·Blood·Tobias NeffHans-Peter Kiem
May 12, 2012·Genetics and Molecular Research : GMR·A M FontesD T Covas
Feb 15, 2007·Expert Opinion on Therapeutic Targets·Alexandre Juillerat, Lucienne Juillerat-Jeanneret
Dec 1, 2001·Expert Opinion on Biological Therapy·R F RousseauH E Heslop
Oct 10, 2007·Expert Opinion on Investigational Drugs·Omar Khan, Mark R Middleton
May 16, 2006·Cancer Treatment Reviews·Cara A RabikM Eileen Dolan
Feb 13, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·N SawaiB P Sorrentino
Jul 5, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Janice E BowmanStanton L Gerson
Dec 19, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·L S LashfordUNKNOWN United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study
May 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stanton L Gerson
Jan 6, 2018·Biomedicines·Ilya O VelegzhaninovOlesya M Vakhrusheva
Feb 28, 2002·The Journal of Pharmacology and Experimental Therapeutics·Colin L SweeneyR Scott McIvor
Aug 16, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Motoo NaganeWebster K. Cavenee

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