Protection of hematopoietic cells against combined O6-benzylguanine and chloroethylnitrosourea treatment by mutant forms of O6-methylguanine DNA methyltransferase.
This report demonstrates that expression of the P140A O6-methylguanine DNA methyl transferase (MGMT) mutant via retrovirus-mediated gene transfer leads to significant, but modest, resistance of cells to both 6-benzylguanine (6-BG) depletion and treatment with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). Expression of the P140A/G156A double mutant appeared to be associated with reduced or unstable protein in hematopoietic cells.
Section of Pediatric Hematology/Oncology, Herman B Wells Center for Pediatric Research, Riley Hospital for Children, Indianapolis, IN, USA.
D A
DA
Williams
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R
Maze
C
C
Kurpad
A
A
Pegg
L C
LC
Erickson
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D002330:Carmustine / Q000009:adverse effects*; D004260:DNA Repair / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D007939:Leukemia L1210 / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D051379:Mice; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic
D000970:Antineoplastic Agents; C064976:O(6)-benzylguanine; D006147:Guanine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002330:Carmustine