Effect of iron as an environmental poisonous compound upon the precocious development of human hepatocellular carcinoma in Myanmar

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The precocious development of hepatocellular carcinoma (HCC) is a crucial problem in Myanmar. As a possible cause, iron incorporated from the environment is implicated. In the present study, we investigated the deposition of iron and the expression of iron-responsive element binding protein (IREBP) in the tissue sections from Myanmar HCC, and then the correlation between these iron-related parameters and HCC cell kinetics under the intimate cooperation with Department of Medical Research (DMR). Actually, we collected cancerous and non-cancerous parts of more than 30 HCC patients at our 3-times visit to Yangon (December 18 to 24, 2001, December 19-28, 2002 and December 18-23, 2003). During our visit, we also' held not only several meetings with DMR and Medical University scientists and but workshops on TUNEL in 2002 and nonradioactive in situ hybridization in 2003 in DMR, which successfully promoted our friendships. When Myanmar HCC tissue sections were examined for iron deposition, we found significantly heavier deposition of iron in Myanmar HCC than that of Japanese one. However, we failed to analyze the expression of IREBP effectively because of the inevitable loss of structural details after microwave retrieval of reactivity. In the study on the HCC cell kinetics, the specimens with a high proliferating activity assessed by Ki-67 staining was correlated with a low frequency of TUNEL positive cells while low proliferative cases were with frequent apoptosis. In the latter case, an apparent association with Fas ligand expression was found. Moreover, when we investigated the liver regeneration kinetics after partial hepatectomy in iron-overloaded rat model, a significant precocious starting of regeneration was observed, accompanying overall increase in the rate of apoptosis. These results indicate that acceleration of hepatocyte turnover by overloaded iron may promote the development of HCC under the proliferation-induced conditions such as viral infection.