title: Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft.
abstract: 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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: S P
authors.initials: SP
authors.lastname: Johnson
authors.forename: Q
authors.initials: Q
authors.lastname: Dong
authors.forename: S C
authors.initials: SC
authors.lastname: Schold
authors.forename: B K
authors.initials: BK
authors.lastname: Rasheed
authors.forename: S H
authors.initials: SH
authors.lastname: Bigner
authors.forename: F
authors.initials: F
authors.lastname: Ali-Osman
authors.forename: E
authors.initials: E
authors.lastname: Dolan
authors.forename: O M
authors.initials: OM
authors.lastname: Colvin
authors.forename: P
authors.initials: P
authors.lastname: Houghton
authors.forename: G
authors.initials: G
authors.lastname: Germain
authors.forename: J T
authors.initials: JT
authors.lastname: Drummond
authors.forename: S
authors.initials: S
authors.lastname: Keir
authors.forename: S
authors.initials: S
authors.lastname: Marcelli
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: P
authors.initials: P
authors.lastname: Modrich
mesh_terms: 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
chemical_list: D009074:Melanocyte-Stimulating Hormones; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase