scholarly journals DNA Damage Induced by DNA Topoisomerase I- and Topoisomerase II- Inhibitors Detected by Histone H2AXphosphorylation in Relation to the Cell Cycle Phase and Apoptosis

Cell Cycle ◽  
2003 ◽  
Vol 2 (6) ◽  
pp. 613-618 ◽  
Author(s):  
Xuan Huang ◽  
Frank Traganos ◽  
Zbigniew Darzynkiewicz
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Topoisomerase I ◽  
Topoisomerase Ii ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Dna Topoisomerase I ◽  
Dna Topoisomerase ◽  
Topoisomerase Ii Inhibitors

DNA Damage Induced by DNA Topoisomerase I- and Topoisomerase II- Inhibitors Detected by Histone H2AX Phosphorylation in Leukemic Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4240-4240
Author(s):  
Dorota H. Halicka ◽  
Xuan Huang ◽  
Fevzi M. Ozkaynak ◽  
Karen Seiter ◽  
Frank Traganos ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Topoisomerase I ◽  
Caspase 3 ◽  
S Phase ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Dna Topoisomerase I ◽  
H2ax Phosphorylation ◽  
Dna Topoisomerase ◽  
Histone H2ax

Abstract Histone H2AX is phosphorylated on Ser-139 by ATM kinase in response to damage that induces dsDNA breaks. Immunocytochemical detection of phosphorylated H2AX (γH2AX), thus, reveals the presence of dsDNA breaks in chromatin. Multiparameter cytometry was presently used to correlate the appearance of γH2AX with: (a) cell cycle phase; (b) caspase-3 activation; and (c) apoptosis-associated DNA fragmentation in individual human leukemic HL-60 cells treated with the DNA topoisomerase I (topo1) inhibitors topotecan (TPT) and camptothecin (CPT) or with the topo2 inhibitor mitoxantrone (MTX). In response to TPT or CPT maximal increase of γH2AX immunofluorescence was seen in S-phase cells by 90 min. In contrast, following MTX treatment the maximal rise of γH2AX was detected at 2 h in G1 cells and the cell cycle phase specificity was much less apparent. A linear relationship between the drug concentration and increase of γH2AX immunofluorescence was seen only up to 200 nM TPT; a decline in γH2AX was apparent at a concentration range between 0.4 and 1.6 μM TPT. Thus, the intensity of γH2AX immunofluorescence, as a marker of cell survival following TPT treatment, can be used only within a limited range of drug concentration. Following treatment with TPT, CPT or MTX the peak of H2AX phosphorylation preceded caspase-3 activation and the appearance of apoptosis-associated DNA fragmentation, both selective to S-phase cells. Progression of apoptosis was paralleled by a decrease in γH2AX immunofluorescence. On the basis of our laboratory results, the present clinical study is evaluating ex vivo the feasibility of assessing DNA damage induced by treatment with topoisomerase inhibitors in patients with acute leukemias.

scholarly journals Mitotic Bypass Via An Occult Cell Cycle Phase Following DNA Topoisomerase II Inhibition In p53 Functional Human Tumor Cells

Cell Cycle ◽  
2007 ◽  
Vol 6 (16) ◽  
pp. 2071-2081 ◽  
Author(s):  
Paul J. Smith ◽  
Nuria Marquez ◽  
Marie Wiltshire ◽  
Sally Chappell ◽  
Kerenza Njoh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Cells ◽  
Topoisomerase Ii ◽  
Human Tumor ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Dna Topoisomerase Ii ◽  
Human Tumor Cells ◽  
Dna Topoisomerase

DNA topoisomerase I and II activities during cell proliferation and the cell cycle in cultured mouse embryo fibroblast (C3H 10T1/2) cells

1985 ◽  
Vol 158 (1) ◽  
pp. 1-14 ◽  
Author(s):  
James V. Tricoli ◽  
Beni M. Sahai ◽  
Patrick J. McCormick ◽  
Sandra J. Jarlinski ◽  
John S. Bertram ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Mouse Embryo ◽  
Topoisomerase I ◽  
Dna Topoisomerase I ◽  
Mouse Embryo Fibroblast ◽  
Dna Topoisomerase
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