![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Molecular Pharmacology, Volume 52, Issue 5, 815-820
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755 Côte Ste. Catherine, Montreal, Quebec, Canada H3T 1E2 (Z.P.C., A.M., A.Mc., D.M., V.B., G.M., L.C.P.), and Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794 (J.R., T.P.B.)
We examined the O6-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 cell lines to BCNU (t = 2.2375, p = 0.0225) but not to UV (t = 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, especially in highly resistant cell lines. ERCC2 may be implicated in this process.
This article has been cited by other articles:
|
|
 |
|
  R. J. Hansen, R. Nagasubramanian, S. M. Delaney, L. D. Samson, and M.E. Dolan Role of O6-methylguanine-DNA methyltransferase in protecting from alkylating agent-induced toxicity and mutations in mice Carcinogenesis, May 1, 2007; 28(5): 1111 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Reed, J. J. Yu, A. Davies, J. Gannon, and S. L. Armentrout Clear Cell Tumors Have Higher mRNA Levels of ERCC1 and XPB Than Other Histological Types of Epithelial Ovarian Cancer Clin. Cancer Res., November 1, 2003; 9(14): 5299 - 5305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-M. Wang, Z.-P. Chen, Z.-Y. Xu, G. Christodoulopoulos, V. Bello, G. Mohr, R. Aloyz, and L. C. Panasci In Vitro Evidence for Homologous Recombinational Repair in Resistance to Melphalan J Natl Cancer Inst, October 3, 2001; 93(19): 1473 - 1478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-P. Chen, Z.-M. Wang, C. A. Carter, M. C. Alley, G. Mohr, and L. C. Panasci Both Extraneuronal Monoamine Transporter and O6-Methylguanine-DNA Methyltransferase Expression Influence the Antitumor Efficacy of 2-Chloroethyl-3-sarcosinamide- 1-nitrosourea in Human Tumor Xenografts J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 712 - 715. [Abstract] [Full Text]
|
|
|
|
|
|
Z.-P. Chen, J. Remack, T. P. Brent, G. Mohr, and L. C. Panasci Extraneuronal Monoamine Transporter Expression and DNA Repair Vis-a-Vis 2-Chloroethyl-3-sarcosinamide-1-nitrosourea Cytotoxicity in Human Tumor Cell Lines Clin. Cancer Res., December 1, 1999; 5(12): 4186 - 4190. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
