![[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}
|
|
|
|
|
||
A Fujimori, M Gupta, Y Hoki and Y Pommier
Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA.
A camptothecin (CPT)-resistant cell line (MCF-7/C4) was established from MCF-7 cells by mutagenic treatment with methylmethanesulfonate and selection with CPT. MCF-7/C4 is 30-fold resistant to CPT and is cross- resistant to UV and cis-dichlorodiammineplatinum(II) but not to VP-16 or ionizing radiation. Topoisomerase I (top1)-mediated cleavable complexes in the presence of CPT, measured by oligonucleotide assay and by alkaline elution, were similar in both cell lines. Other top1 parameters such as top1 protein, RNA levels, and DNA relaxation were also similar in both cell lines. Thus, CPT resistance is not due to alterations in top1 activity but is caused by changes in the downstream pathways from the top1-induced damage. Both cell lines had similar doubling time (22 hr), but MCF-7/C4 cells showed reduced S-phase fraction in the absence of CPT and reduced G2 delay after CPT treatment. p53, GADD45, and p21WAF1/CIP1 were induced similarly by CPT in both cell lines. The overall repair capacity estimated by the ability of cells to reactivate UV-damaged pSV-CAT plasmid was increased in MCF-7/C4 cells. These observations suggest that enhanced DNA repair is one of the factors involved in CPT resistance.
This article has been cited by other articles:
|
|
 |
|
  L.-C. Ma, C.-C. Kuo, J.-F. Liu, L.-T. Chen, and J.-Y. Chang Transcriptional Repression of O6-Methylguanine DNA Methyltransferase Gene Rendering Cells Hypersensitive to N,N'-Bis(2-chloroethyl)-N-nitrosurea in Camptothecin-Resistant Cells Mol. Pharmacol., August 1, 2008; 74(2): 517 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Liao, R. W. Robey, J. Guirouilh-Barbat, K. K. W. To, O. Polgar, S. E. Bates, and Y. Pommier Reduced Expression of DNA Topoisomerase I in SF295 Human Glioblastoma Cells Selected for Resistance to Homocamptothecin and Diflomotecan Mol. Pharmacol., February 1, 2008; 73(2): 490 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Kuo, J.-F. Liu, and J.-Y. Chang DNA Repair Enzyme, O6-Methylguanine DNA Methyltransferase, Modulates Cytotoxicity of Camptothecin-Derived Topoisomerase I Inhibitors J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 946 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kruczynski, J.-M. Barret, B. van Hille, N. Chansard, J. Astruc, Y. Menon, C. Duchier, L. Creancier, and B. T. Hill Decreased Nucleotide Excision Repair Activity and Alterations of Topoisomerase II{alpha} Are Associated with the in Vivo Resistance of a P388 Leukemia Subline to F11782, a Novel Catalytic Inhibitor of Topoisomerases I and II Clin. Cancer Res., May 1, 2004; 10(9): 3156 - 3168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Park, W. Lam, and Y.-c. Cheng X-ray Repair Cross-Complementing Gene I Protein Plays an Important Role in Camptothecin Resistance Cancer Res., January 1, 2002; 62(2): 459 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bomgaars, S. L. Berg, and S. M. Blaney The Development of Camptothecin Analogs in Childhood Cancers Oncologist, December 1, 2001; 6(6): 506 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Shah and G. K. Schwartz Cell Cycle-mediated Drug Resistance: An Emerging Concept in Cancer Therapy Clin. Cancer Res., August 1, 2001; 7(8): 2168 - 2181. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
