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Titolo:
EVIDENCE FOR NUCLEOTIDE EXCISION-REPAIR AS A MODIFYING FACTOR OF O-6-METHYLGUANINE-DNA METHYLTRANSFERASE-MEDIATED INNATE CHLOROETHYLNITROSOUREA RESISTANCE IN HUMAN TUMOR-CELL LINES
Autore:
CHEN ZP; MALAPETSA A; MCQUILLAN A; MARCANTONIO D; BELLO V; MOHR G; REMACK J; BRENT TP; PANASCI LC;
Indirizzi:
SIR MORTIMER B DAVIS JEWISH HOSP,LADY DAVIS INST MED RES,3755 COTE STE CATHERINE MONTREAL PQ H3T 1E2 CANADA SIR MORTIMER B DAVIS JEWISH HOSP,LADY DAVIS INST MED RES MONTREAL PQ H3T 1E2 CANADA ST JUDE CHILDRENS HOSP,DEPT MOL PHARMACOL MEMPHIS TN 38105
Titolo Testata:
Molecular pharmacology
fascicolo: 5, volume: 52, anno: 1997,
pagine: 815 - 820
SICI:
0026-895X(1997)52:5<815:EFNEAA>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALKYLATING-AGENTS; DNA-REPAIR; XERODERMA-PIGMENTOSUM; MAMMALIAN-CELLS; DAMAGED DNA; SENSITIVITY; ALKYLTRANSFERASE; EXPRESSION; ERCC2; GENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
Z.P. Chen et al., "EVIDENCE FOR NUCLEOTIDE EXCISION-REPAIR AS A MODIFYING FACTOR OF O-6-METHYLGUANINE-DNA METHYLTRANSFERASE-MEDIATED INNATE CHLOROETHYLNITROSOUREA RESISTANCE IN HUMAN TUMOR-CELL LINES", Molecular pharmacology, 52(5), 1997, pp. 815-820

Abstract

We examined the O-6-methylguanine-DNA methyltransferase (MGMT) protein as well as MGMT activity levels and the excision repair cross-complementing rodent repair deficiency gene, ERCC2 (XPD), protein levels in 14 human tumor cell lines not selected for chloroethylnitrosourea (CENU) resistance. These results were compared with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) cytotoxicity and UV light sensitivity. MGMT protein correlated significantly with MGMT activity (r = 0.9497, p = 0.0001). There was no significant linear correlation between BCNU cytotoxicity and MGMT content as determined by both Western analysis (r = 0.139, p = 0.6348) and activity assay (r = 0.131, p = 0.6515). However, MGMT-rich cell lines were found to be more resistant than MGMT-poor celllines to BCNU (t = 2.2375, p = 0.0225) but not to UV (f = 1.1734, p =0.1317). Furthermore, the most BCNU-sensitive cell lines were all MGMT-poor. UV sensitivity was significantly correlated to BCNU cytotoxicity (r = 0.858, p = 0.0001). Significant correlations were found between ERCC2 protein levels and BCNU cytotoxicity (r = 0.786, p = 0.0009) or UV sensitivity (r = 0.874, p = 0.0001). Our results confirm that MGMT plays an important role in CENU resistance, but not in UV resistance. The correlation of UV sensitivity with BCNU cytotoxicity suggests that nucleotide excision repair is an important modifying factor of MGMT-mediated innate CENU resistance in human tumor cell lines, especiallyin highly resistant cell lines. ERCC2 may be implicated in this process.

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Documento generato il 21/09/20 alle ore 17:51:41