Accumulation of copper and generation of hydroxyl radicals of hepatocellular carcinoma

Aims: This study evaluated the connection between the progression of hepatic fibrosis and trace metals, the distribution profiles of copper(Cu) and Zinc (Zn) and the generation of hydroxyl radicals from Cu- metallothionein (MT) purified from human hepatocellular carcinoma (HCC). Methods: We measured the metal contents in HCC tissue and liver parenchyma in patients with HCC. The content of metals in the liver was measured by particle induced X-ray emission (PIXE). Distribution profiles of Cu and Zn in human liver was evaluated by high-performance liquid chromatography (HPLC). The generation of hydroxyl radicals was measured by electron spin resonance (ESR) spin-trapping technique. Results: Hepatic copper content increased with the progression of hepatic fibrosis. Copper level in liver parenchyma was higher in patients with HCC than in those without HCC (p < 0.01). MT was mainly present as Zn-MT in normal liver, Cu,Zn-MT in surrounding liver parenchyma and Cu-MT in HCC (p < 0.01). The signal intensity of the ESR spectrum in HCC was stronger than those in normal liver and surrounding liver parenchyma. Conclusions: Copper accumulation in the liver parenchyma seems to relate to hepatocarcinogenesis.

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