Induction of DNA-protein cross-links by platinum compounds

Citation
K. Wozniak et Z. Walter, Induction of DNA-protein cross-links by platinum compounds, Z NATURFO C, 55(9-10), 2000, pp. 731-736
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
ZEITSCHRIFT FUR NATURFORSCHUNG C-A JOURNAL OF BIOSCIENCES
ISSN journal
0939-5075 → ACNP
Volume
55
Issue
9-10
Year of publication
2000
Pages
731 - 736
Database
ISI
SICI code
0939-5075(200009/10)55:9-10<731:IODCBP>2.0.ZU;2-F
Abstract
The differences between cis- and trans-diamminedichloroplatinum II (DDP) in forming DNA-protein cross-links in isolated human lymphocytes were investi gated. Both cis- and trans-DDP can induce DNA-protein cross-links. We show that cis-DDP forms complexes between DNA and proteins faster than trans-DDP . This results from an increase in the quantity of DNA and platinum togethe r with an increase in drug concentration. Under the same conditions trans-D DP causes a decrease in DNA-forming complexes with proteins. After a 12 h i ncubation of lymphocytes we observe a similar level of DNA in DNA-protein c rosslinks induced by DDP isomers, but more platinum appears in complexes in duced by trans-DDP. The results obtained demonstrate that the antitumor dru g - cis-DDP and the clinically ineffective trans-DDP induce links between D NA and proteins in a different manner. We suggest that the therapeutic acti vity of cis-DDP can in part arise from rapidly forming DNA-protein complexe s which can destroy the most important cellular processes, such as replicat ion and transcription.