الفهرس 
Aim of the workOnly 14 pages are availabe for public view
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Abstract
The present study attempted to investigate the effect of copper (II) Girard’s T complex on DNA both in vitro and in vivo. This was done to examine its ability to be used as anti-tumor agent. Firstly, The effect of copper (II) Girard’s T complex was studied in vitro. Several experiments undergone to study the reaction between copper (II) Girard’s T complex and DNA including: 1- Electrophoresis technique showed that the copper (II) Girard’s T complex intercalates with DNA molecule with a noticeable breakage effect and two fragments were obtained. 2- UV-Vis Spectroscopy highlighted the effect of complex on DNA. λmax of DNA shifted to longer wavelength accompanied by a hyperchromic shift. Also, the λmax of the complex shifted to shorter wavelength. 3- Different conditions affecting the reaction at λmax were studied such as the molar ratio between DNA molecule and Cu (II) Girard’s T complex in the formed compound, pH, time and temperature. The effect of time was studied using UV-Vis spectroscopy and confirmed by electrophoresis. It was noticed that the reaction between copper (II) Girard’s T complex and DNA was completed after 60 minutes. Also, both UV-Vis spectroscopy and electrophoresis techniques led to the indication that increasing temperature up to 55-60˚C caused degradation of the fragment of high molecular weight that was obtained in the early electrophoresis experiment. This fragment is reformed after cooling. 4- The effect of ligand (Girard’s T), metal ion (Cu2+) and the complex was studied separately on DNA by two methods: electrophoresis and fluoremetry. The two methods showed that the more intercalation, the more delay in the electrophoretic mobility and hence the fluorescence quenching of the DNA bound ethidium ion. The more fluorescence quenching and retardation of the electrophoretic mobility was obtained in order of the metal ion (Cu2+) > complex > ligand ( Girard’s T). 5- IR spectrum of the reaction mixture showed a shift in the carbonyl frequency of DNA base at 1692 cm-1 to 1678 cm¬¬-1. This indicates that the reaction takes place through the carbonyl of C6 in guanine and carbonyl of C2 in cytosine in DNA moelcule. Secondly, the effect of copper (II) Girard’s T complex was studied in vivo as follows: I-Effect of copper (II) Girard’s T complex on EAC cells of tumor-bearing mice. The mice were classified into two groups: control non-treated tumor-bearing mice and tumor-bearing mice treated for nine days with a daily dose of 10mg/kg copper (II) Girard’s T complex beginning 24 hours after inoculation of the tumor. The following parameters were determined: Survival of tumor-bearing mice, tumor volume, and tumor cell viability. These parameters represent a good evidence for the antitumor activity of the complex under study. II-Effects of copper (II) Girard’s T complex on growth and DNA synthesis of EAC cells. The following results were obtained:
1-The mean survival time increased from 15.5±0.58 days for non-treated tumor-bearing mice to 24.27±0.96 for tumor-bearing mice treated with copper (II) Girard’s T complex. 2-The treatment of tumor-bearing mice with copper (II) Girard’s T complex caused significant reduction in tumor volume and EAC cells viability compared to that of non-treated tumor-bearing mice. 3- Pattern of DNA extracted from EAC cells of tumor-bearing mice treated with the copper (II) complex showed DNA breakage.
4-DNA histograms of both the non-treated and treated groups gave the indication that treatment with copper (II) Girard’s T complex led to DNA diploid cell population instead of aneuploidy in the non-treated group. from the present study, it may be concluded that: 1-Copper (II) Girard’s T complex is an efficient antitumor agent in the Ehrlich ascites carcinoma model of cancer. The antitumor activities of this complex are attributed to its effect on DNA (in vitro and in vivo). 2-This complex may act as antitumor material since it inhibited the growth and DNA synthesis of EAC cells.
Future work is planned to use this complex as antitumor drug in other tumor cancers.