New insights in the cellular processing of platinum antitumor compounds, using fluorophore-labeled platinum complexes and digital fluorescence microscopy

2000 ◽  
Vol 5 (5) ◽  
pp. 655-665 ◽  
Author(s):  
Chris Molenaar ◽  
Jan-Maarten Teuben ◽  
Robert J. Heetebrij ◽  
Hans J. Tanke ◽  
Jan Reedijk
2005 ◽  
Vol 3 (3-4) ◽  
pp. 179-190 ◽  
Author(s):  
Markus Galanski ◽  
Susanna Slaby ◽  
Michael A. Jakupec ◽  
Bernhard K. Keppler

In order to develop platinum complexes with selective activity in primary and secondary bone malignancies and with the aim to optimize antitumor activity, platinum(II) complexes with aminotris(methylenephosphonic acid) as bone-seeking (osteotropic) ligand have been synthesized, characterized and tested in the cisplatin-sensitive ovarian carcinoma cell line CH1. As non-leaving diamine ligands, which are decisive for the cellular processing of DNA adducts,cis-R,S-cyclohexane-1,2-diamine,trans-S,S-cyclohexane-1,2-diamine andtrans-R,R-cyclohexane-1,2-diamine have been used, resulting in complexes 1, 2, and 3, respectively. The cytotoxicity of the complexes under investigation decreases in the order 3>2>1 which is in accord with structure-activity relationships with other (cyclohexane-1,2- diamine)platinum(II) and platinum(IV) complexes: Bothtranscomplexes (2 and 3) display a higherin vitropotency than the correspondingcisisomer (I), with thetrans-R,Risomer (3) being the most active in this series. In comparison to the analogous (cyclohexane-1,2-diamine)platinum(II) complexes with bis(phosphonomethyl)aminoacetic acid as osteotropic carrier ligand, the cytotoxicity of 1-3 was found to be 1.5 – 2 fold higher, which is explainable by a different coordination mode of the phosphonic acid ligands (acetato versus phosphonato).


1990 ◽  
Vol 18 (5) ◽  
pp. 938-938 ◽  
Author(s):  
IAN E. G. MORRISON ◽  
CATHERINE M. ANDERSON ◽  
GEORGE N. GEORGIOU ◽  
RICHARD J. CHERRY

2020 ◽  
Vol 24 (10) ◽  
pp. 1103-1105
Author(s):  
D. Chesov ◽  
V. Lesanu ◽  
N. Ciobanu ◽  
A. Codreanu ◽  
V. Crudu ◽  
...  

1993 ◽  
Vol 105 (2) ◽  
pp. 541-550 ◽  
Author(s):  
A.B. Hassan ◽  
P.R. Cook

Sites of DNA replication in nuclei are focally concentrated, suggesting that an underlying structure organizes the activity of many polymerases. As fixation could induce aggregation into foci, we examined the distribution of replication sites in unfixed nuclei. HeLa cells were encapsulated in agarose microbeads, permeabilized in a ‘physiological’ buffer, their DNA polymerizing activity characterized, and replication sites directly labelled by incubation with fluorochrome-dUTP conjugates. Using conventional and digital fluorescence microscopy, 80–250 foci were seen in these unfixed cells. These foci are unlikely to be formed by the aggregation of separate polymerases as most replication activity found in vivo is retained throughout these procedures. Although commonly used fixation methods collapsed or dispersed their periphery, the central core was very stable. Foci remained when approximately 90% chromatin was removed, suggesting they were attached to an underlying structure.


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