SarCNU mediates selection of P140K methylguanine-DNA-methyltransferase transduced human CD34(+) cells in vitro.
The therapeutic combination O(6)-benzylguanine (BG) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) can be used to select for P140K methylguanine-DNA-methyltransferase (P140K MGMT) transduced hematopoietic progenitors both in vitro and in vivo. SarCNU is a new alkylating agent which has advantages over BCNU. We tested the ability of P140K MGMT transduced human CD34(+) cells to resist SarCNU treatment and be selected for in vitro. BG/SarCNU exposure led to an increase in the proportion of transduced cells from 13 to 27%. The IC(90) was increased sixfold by P140K MGMT transduction. These results suggest that SarCNU may be a suitable agent for in vivo selection strategies.
Zielske
Steven P
SP
Molecular Virology Program, Division of Hematology/Oncology and Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Gerson
Stanton L
SL
D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000494:pharmacology; D002330:Carmustine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002469:Cell Separation / Q000379:methods*; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020125:Mutation, Missense; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods*
D018952:Antigens, CD34; D000970:Antineoplastic Agents; C044565:2-((((2-chloroethyl)nitrosoamino)carbonyl)amino)propanamide; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002330:Carmustine