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Abstract The present study, was carried out to evaluate the anticancer activity of CNPs either alone or combined with γ-irradiation. As tumor have systemic effects on the host, studying the antioxidant status for tumor, liver, kidney and spleen, angiogenic growth factors (TNF-α, PDGF and VEGF). Also, histopathological and apoptotic examination of tumor, liver, kidney, and spleen tissues were performed to evaluate the histopathological and apoptotic changes. In vitro the cytotoxicity of nanoparticles not only led to the death of Ehrlich carcinoma cells, but also led to brust of these dead cells at certain doses. Nanoparticles led to rupture of cells content after their death. The median lethal concentration of CNPs was 20 μg/ml for Ehrlich carcinoma cells. In vivo experiments were performed on healthy and Ehrlich carcinoma-bearing female Swiss albino mice. Mice were randomly assigned and equally divided into 5 experimental groups of 10 mice each as follows: Control group: the mice were neither treated nor irradiated. Tumor-bearing group: each mouse in this group was inoculated subcutaneously with 0.2 ml of EAC cells (2.5x106 cells) for solid tumor induction. The animals were left without any treatment till the end of the experiment. Tumor bearing-CNPs group: Mice in this group were orally treated with CNPs (0.5 mg/kg b.wt.) daily, for 15 successive days from the 7th day after inoculation of EAC. Tumor- Bearing-Irradiated group: Each mouse in this group was inoculated subcutaneously with EAC cells and each tumor-bearing mouse was exposed to γ-radiation 0.25 Gy×2/week for two weeks Tumor- Bearing-CNPs-Irradiated group: in these group mice bearing solid tumor was orally supplemented with CNPs and exposed to γ-radiation. The results obtained can be summarized as follows Studying the systemic effects of the tumor on the host showed that, the presence of tumor resulted in disequilibria of the antioxidant defense system including decrease in GSH content and increase in LPO in liver, kidney and spleen tissue. Treatment of mice bearing tumor with CNPs induced tumor growth regression by decreasing the level of the angiogenic factors (TNF-α, PDGF and VEGF) and increase LPO content in the tumor tissue. In the tumor tissue the histopathological Examinations recorded that treatment of female mice bearing Ehrlich carcinoma with CNPs and or low doses of γ-irradiation recorded great destruction of tumor tissue. Also, apoptotic and necrotic recorded that treatment of female mice bearing Ehrlich carcinoma with CNPs and or low doses of γ- irradiation represented necrotic regions, and vacuolated areas.the other hand, the results obtained in the present study revealed that subcutaneous (s.c) transplantation of EAC cells on the back of neck region of the experimental mice produced a high significant increase of LPO level and decrease in GSH level in liver, kidney and spleen was observed in comparison with the NC values. Treatment of the experimental mice-bearing solid Ehrlich tumor with CNPs and or low doses of γ-irradiation revealed decrease in LPO and increase in GSH contents of liver, kidney and spleen by compared to EC-bearing group. Histopathological Examination of liver sections of mice bearing Ehrlich carcinoma showed accumulation of Ehrlich carcinoma cells (ECs) around congested portal blood vessels with completely haemolysed red blood cells (RBCs) in the portal vein. On the other hand, treatment of the experimental mice-bearing solid Ehrlich tumor with CNPs and or low doses of γ-irradiation revealed great disappearance of metastatic Ehrlich carcinoma cells. Great dilatation and wideness of the central vein was also observed and disappearance of metastatic Ehrlich cells were observed in liver of Ehrlich carcinoma chitosan nanoparticles and irradiation treated group. Apoptotic and necrotic examinations in our study treatment of female mice bearing Ehrlich tumor with CNPs represented low amount of sporadic late apoptosis in liver hepatocytes and presence of green viable hepatocytes. However treatment of mice bearing Ehrlich carcinoma with CNPs and or low doses of γ-irradiation represented high infestations of sporadic necrotic cells in between the hepatic cells and apoptotic cells infiltrated between the hepatocytes and encircled the portal hepatic vein. Histopathological examination of kidney in present study showed normal appearance of kidney was recorded when experimental animals bearing Ehrlich carcinoma treated by CNPs and low doses of γ- radiation. However, CNPs treatment represented disappearance of tumor cells metastasis, bleeding appearance and degenerated glomerulus. On the other hand CNPs and exposure to low doses of γ- radiation represented great disappearance of tumor cells metastasis and less occurrence of degenerated glomerulus. Apoptotic and necrotic examination early and late apoptosis were recorded in some of convoluted cell in kidneys of mice bearing Ehrlich carcinoma exposed to low doses of γ- radiation. Late apoptotic state in glomerulus and convoluted tubules cells was shown in mice bearing Ehrlich carcinoma and treated by 0.5 mg/kg CNPs or treated by CNPs and exposed to low doses of γ- radiation. Histopathologecal examination of spleen tissue in mice bearing EC represented many megakaryocytes in its white pulp. Treatment of mice bearing EC with CNPs represented small infraction in peripheral zone, apoptotic cells and megacryocytes cells in marginal zone and red pulp of the spleen tissue section. Spleen tissue section of mice bearing EC and exposed to γ-irradiation predict splenic faintly stained nodule of white pulp. Its red pulp represented increase extramedullary hematopoiesis, erythyroid and myeloid precursors and large number of megakaryocytes. On the other hand, exposure of female mice bearing EC treated by CNPs to γ- radiation represented normal appearance of white pulp, giant megakaryocytes in the marginal zone and megakaryocytes in the red pulp. Apoptotic and necrotic examination of spleen tissue of female mice bearing EC treated with CNPs showed regions had necrotic in the red pulp. However, exposure of female mice bearing EC to γ- irradiation represented the normal appearance of vital spleen tissue region layers. On the other hand, the combined treatments of mice bearing EC with CNPs and γ- irradiation showed empty regions in whit pulp and some underwent apoptotic cells in red pulp. |