الفهرس 
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Abstract
Hepatocellular carcinoma (HCC) shows a dramatic increase of its incidence worldwide over the last three decades and is associated with a very poor prognosis. Except for patients accessible for surgical therapy, the 5-year survival is less than 3%. Diagnosis is usually made at an advanced stage of the disease, and poorly differentiated tumors are sometimes a challenge for liver-pathologists.
Many types of cancers have an abnormal control of the transition from G1 to S phase of the cell cycle. P16 gene is a tumor suppressor gene because it is frequently silenced by deletion or inactivating mutation in human cancers.
This gene is located on chromosome 9 p 21 and encodes a G1 cyclin-dependent kinase (CDK) inhibitor that can interrupt the tumor cycle by acting as a tumor suppressor gene and induces G1 cell cycle arrest. Loss of its function can lead to uncontrolled cell proliferation. P16 gene was reported to be extensively methylated in patients with HCC. Indeed, methylation of P16 was found not only in HCC, but also in patients with chronic liver disease.
We aimed in our study to assess the methylation status and the expression of P16 in induced HCC in rats. In our study we induce HCC in rats. group 1 was acting as control. group 2 was injected by DEN once. group 3 with subjected to phenobarbital in drinking water for 14 weeks. group 4 was injected with DEN then subjected to phenobarbital in drinking water.
The liver tissue was analyzed for the methylation status of P16 promoter using methylation specific PCR and its expression was assessed using real time RT PCR. The histopathological features of the HCC changes in the liver tissue were determined by haematoxylin and eosin staining of the liver tissue.
Our results showed that P16 methylation status was increased and consequently its expression was decreased in HCC group induced by both DEN and phenobarbital than HCC groups induced by each of them alone.
We conclude that the expression of P16 could be used as a predictor to appearance of malignant changes.