![[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}
|
|
|
|
|
||
FA Fornari, JK Randolph, JC Yalowich, MK Ritke and DA Gewirtz
Department of Medicine, Medical College of Virginia, Richmond 23298.
The capacity of doxorubicin to inhibit topoisomerase II in the MCF-7 breast tumor cell line is supported by the induction of protein- associated single-strand breaks in DNA, as well as by interference with the decatenation activity of nuclear extracts. Doxorubicin also produces non-protein-associated DNA strand breaks (at a supraclinical concentration of 5 microM), which may indicate damage mediated via the generation of free radicals. However, no strand breaks are detected in DNA of MCF-7 cells at the IC50 for doxorubicin (approximately 0.1 microM). At doxorubicin concentrations of 0.05, 0.1, and 0.5 microM, at which growth is inhibited by approximately 15, 50, and 75%, respectively, doxorubicin interferes with radiation-induced unwinding of DNA; doxorubicin also produces a concentration-dependent inhibition of DNA synthesis that corresponds closely to growth inhibition. These studies suggest that DNA strand breaks fail to fully account for the antiproliferative activity of doxorubicin in the MCF-7 breast tumor cell line. Compromised DNA synthesis associated with interference with DNA unwinding may contribute to growth inhibition in MCF-7 cells exposed to doxorubicin.
This article has been cited by other articles:
|
|
 |
|
  P. D. Ottewell, H. Monkkonen, M. Jones, D. V. Lefley, R. E. Coleman, and I. Holen Antitumor Effects of Doxorubicin Followed by Zoledronic Acid in a Mouse Model of Breast Cancer J Natl Cancer Inst, August 20, 2008; 100(16): 1167 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Ottewell, B. Deux, H. Monkkonen, S. Cross, R. E. Coleman, P. Clezardin, and I. Holen Differential Effect of Doxorubicin and Zoledronic Acid on Intraosseous versus Extraosseous Breast Tumor Growth In vivo Clin. Cancer Res., July 15, 2008; 14(14): 4658 - 4666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Gewirtz, X. Di, T. D. Walker, and S. T. Sawyer Erythropoietin fails to interfere with the antiproliferative and cytotoxic effects of antitumor drugs. Clin. Cancer Res., April 1, 2006; 12(7): 2232 - 2238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Doroshow, T. W. Synold, G. Somlo, S. A. Akman, and E. Gajewski Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin Blood, May 1, 2001; 97(9): 2839 - 2845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Larson and J. T. Drummond Human Mismatch Repair and G{middle dot}T Mismatch Binding by hMutSalpha in Vitro Is Inhibited by Adriamycin, Actinomycin D, and Nogalamycin J. Biol. Chem., March 23, 2001; 276(13): 9775 - 9783. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
