Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.
A methylator-resistant human glioblastoma multiforme xenograft, D-245 MG (PR), in athymic nude mice was established by serially treating the parent xenograft D-245 MG with procarbazine. D-245 MG xenografts were sensitive to procarbazine, temozolomide, N-methyl-N-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, 9-aminocamptothecin, topotecan, CPT-11, cyclophosphamide, and busulfan. D-245 MG (PR) xenografts were resistant to procarbazine, temozolomide, N-methyl-N-nitrosourea, and busulfan, but they were sensitive to the other agents. Both D-245 MG and D-245 MG (PR) xenografts displayed no O6-alkylguanine-DNA alkyltransferase activity, and their levels of glutathione and glutathione-S-transferase were similar. D-245 MG xenografts expressed the human mismatch repair proteins hMSH2 and hMLH1, whereas D-245 MG (PR) expressed hMLH1 but not hMSH2.
Friedman
H S
HS
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Johnson
S P
SP
Dong
Q
Q
Schold
S C
SC
Rasheed
B K
BK
Bigner
S H
SH
Ali-Osman
F
F
Dolan
E
E
Colvin
O M
OM
Houghton
P
P
Germain
G
G
Drummond
J T
JT
Keir
S
S
Marcelli
S
S
Bigner
D D
DD
Modrich
P
P
D000818:Animals; D019175:DNA Methylation; D004260:DNA Repair; D004351:Drug Resistance; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000032:analysis; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018895:Microsatellite Repeats; D009368:Neoplasm Transplantation; D019853:O(6)-Methylguanine-DNA Methyltransferase; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D009074:Melanocyte-Stimulating Hormones; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase