الفهرس 
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Abstract
The present study aimed to investigate the antitumor effect of biologically synthesized copper nanoparticles (CuNPs) coated by chrysin (5,7-dihydroxyflavone) and/or low dose of gamma radiation (0.5 Gy) against Ehrlich solid tumor in female mice.
Copper nanoparticles were characterized by transmission electron microscopy (TEM), fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-VIS) spectroscopy, dynamic light scattering (DLS) technique, and phase and crystallinity X-ray diffraction (XRD) analysis. The results showed that CuNPs were of size ranging of 21.19-70.79 nm. FTIR analysis of CuNPs showed shifting in the wave number of chrysin’s functional groups due to their involvement in CuNPs synthesis and capping. UV-VIS scan revealed CuNPs absorption peak at 273 nm. DLS technique revealed that CuNPs size ranging of 18.92-412.5 nm. XRD analysis showed intense and sharp peaks revealed that CuNPs were crystalline in nature. The XRD peaks corresponded to pure Cu, CuO and Cu2O.
In vitro study of CuNPs on human breast cancer (MCF-7) cell line showed cytotoxic effect with IC50 of 57.2±3.1 μg/ml. In vivo study revealed that, LD50 of CuNPs was calculated as 6.67
mg/kg b.w. Evaluation of the antitumor effect of CuNPs and/or low dose of gamma radiation in vivo was carried out using eighty female Swiss albino mice randomly divided into eight equal groups as follows:
Group1 (Control (C)): mice were intraperitoneally (i.p.) injected with 0.2 ml of sterile saline on the first day.
Group2 (CuNPs): mice were (i.p.) injected with 0.2 ml (0.667 mg/kg b.w.) of prepared CuNPs starting from the 7th day daily for 2 weeks (5 times each week).
group 3 (Radiation (R)): mice whole body were irradiated with a single dose of (0.5 Gy) gamma radiation once on the 8th day.
group 4 (CuNPs+R): mice were (i.p.) injected with CuNPs as described in group 2 followed by gamma irradiation once as mentioned in group 3.
group 5 (Ehrlich solid carcinoma (EC)): mice were intramuscularly (i.m.) inoculated with 0.2 ml of Ehrlich ascites carcinoma cells (contains 2.5×106 viable EAC cells) in the right thigh of the lower limb on the first day.
group 6 (EC+CuNPs): EC-bearing mice as group 5 were (i.p.) injected with CuNPs daily starting from the 7th day of EAC inoculation as described in group 2.
group 7 (EC+R): EC-bearing mice as group 5 were exposed to gamma irradiation once at the 8th day of EAC inoculation as described in group 3.
group 8 (EC+CuNPs+R): EC-bearing mice as group 5 were (i.p.) injected with CuNPs daily starting from the 7th day of EAC inoculation as described in group 2 followed by gamma irradiation once at the 8th day as described in group 3.
After 21 days of EAC inoculation mice were sacrificed, blood was collected from heart puncture and tumor tissues were dissected.
Results revealed that Ehrlich solid tumor induced significant increase in serum ALT activity and serum creatinine level compared to control group. Moreover, Ehrlich tumor revealed an elevation in calcium concentration, GSH content, CAT activity, as well as gene expression of NF-κB, p38 MAPK, and cyclin D1, while revealed a reduction in MDA level and caspase-3 concentration of untreated tumor tissue.
Ehrlich tumor-bearing mice treated with CuNPs and low dose γ-radiation significantly reduced tumor volume, serum ALT activity, and creatinine level. Furthermore, CuNPs and radiation treated groups showed significant decrease in calcium concentration, GSH content, and CAT activity, as well as down-
regulated gene expression of NF-κB, p38 MAPK, and cyclin D1, while significantly increased MDA level and caspase-3 concentration in the treated tumor tissue compared to the untreated EC tumor-bearing group.
Histopathological examination revealed that combined treatment of CuNPs with low dose of gamma radiation exposure had the most effective influence in tumor tissue damage in comparison with each treatment alone.