الفهرس 
Factors Involved in Cancer DevelopmentOnly 14 pages are availabe for public view
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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.