Abstract: BACKGROUND AND AIM: To investigate the expression and alterations of hypoxia inducible factor-1α (HIF-1α) during development of hepatocellular carcinoma(HCC). MATERIALS AND METHODS: Rat hepatoma model was established with 2-fluorenylacetamide (2-FAA) containing-feeds for 12 weeks in male Sprague-Dawley (SD) rats. Morphological changes in rat livers were examined by HE staining. The changes of HIF-1α in rat livers and sera were quantitatively analyzed by enzyme linked immunosorbent assay (ELISA). Simultaneously, the expression and cellular distribution of liver HIF-1α were assessed by immunohistochemistry. RESULTS: Rat hepatocytes showed granule-like degeneration to atypical hyperplasia and HCC development after ingestion of 2-FAA, with progressive increase of hepatic HIF-1α expression during the course. The levels of HIF-1α in hepatoma tissues and sera were significantly higher than those in normal and degenerative tissues. Immunohistochemistry evidence showed positive expression and hepatocyte distribution of HIF-1α in rat hepatoma. A positive relationship of HIF-1α level in hepatoma tissues and sera was found(r=0.474,P<0.05). CONCLUSION: Hepatic HIF-1α may participate in hepatocytic malignant transformation. Detection of HIF-1α expression during HCC development could be a useful molecular marker for early diagnosis and prognosis of HCC.

Key words: hepatocellular carcinoma, HIF-1α, immunohistochemistry, malignant transformation