الفهرس 
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Abstract
Chronic CCl4 intoxication produced a marked increase in collagen deposition around the portal chord, also nodules of hepatocytes surrounded by variable size of collagen bands were frequently observed, the normal architecture was lost and extended necrotic areas were present. Data coming from our animal model of liver injury proved that the intraperitonealy injected rats by 1:3 CCL4 in olive oil (0.5ml/kg) body weight 2 times aweek for 8 weeks exhibited 4th stage liver fibrosis and early stage liver cirrhosis and high expression of both telomerase and cytokeratin20 genes.To evaluate the use of TERT and CK20 gene expression as a diagnostic tool for HCC in animal model, thirty adult albino male rats were divided into 3 groups of 10 animals each. Animals in group A underwent a sham experiment, group B was injected by CCL4 for 4 weeks (early group) and group C was injected by CCL4 for 8 weeks (late group). At the end of the experiment, specimens from liver were all stained by H&E dye. TERT and CK20 gene expression were done by Real-Time PCR in blood and tissue samples. The relative quantification of target genes and statistical analysis were done. A histopathological study of rat liver of early group was marked mild fibrosis and the late group showed formation of cirrhotic nodule with dysplasia of hepatocytes. TERT mRNA was increased significantly in early and late tissue by about 6.86 and 9.67 folds and in blood samples, the expression was increased about 3.55 and 12.88 folds, respectively. The gene expression of CK20 was not observed in blood stream but was expressed significantly in tissues with about 2.98 and 32.32 folds. P value was <0.001 between control and early or late HCC. Human TERT gene expression was observed to increase according to HCC in both tissue and blood samples but CK20 was up regulated in tissue samples.In the case of experimental animal models, Carbon tetrachloride (CCL4) is a widely used hepatotoxic agent in rodents and its trichloromethyl radical (CCL3) induced toxicity which closely resembles human cirrhosis. Hence, it is an acceptable animal model for characterizing hepatoprotective activity. The early diagnosis for HCC will increase the potential for curative treatment and improves survival rate. For early diagnosis of HCC, blood is the best source for revelation of cancer related biomarkers. Telomerase reverse transcriptase (TERT) is a ribonucleoprotein which maintains telomere length and blocks inconvenient repair of natural ends of linear chromosomes. Dysfunction of telomerase is responsible for failure of tissue repair or regeneration. High telomerase activity was found in a high percentage of several cancer cells, so the level of this enzyme may represent a type of cancer marker, the importance of quantification of telomerase activity in the diagnosis of small HCC and in the assessment of treatment has been reported. Although normal cells have some active telomerase, increased expression of telomerase produce probability of developing cancer cells. Tumors require maintenance of telomere stability for their long term proliferation, so escape from cellular senescence by activating telomerase and this represents an additional step in oncogenesis that most tumors require for proliferation. CK20 is a low molecular weight cytokeratin distributed in epithelia and their neoplasm. CK 20 is an established tumor marker.