Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma

Ebara, Masaaki; Fukuda, Hiroyuki; Hatano, Ryouji; Saisho, Hiromitsu; Nagato, Yoshinori; Suzuki, Keiji; Nakajima, Katuyuki; Yukawa, Masae; Kondo, Fukuo; Nakayama, Akihiro; Sakurai, Hiromu

« Previous Next »Journal of Hepatology
Volume 33, Issue 3 , Pages 415-422, September 2000

Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma

Masaaki Ebara
- Masaaki Ebara, First Department of Medicine, School of Medicine, Chiba University 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8677, Japan. Tel: 81 43 226 2084. Fax: 81 43 226 2088.
- First Department of Medicine, School of Medicine, Chiba UniversityJapan
Hiroyuki Fukuda
- First Department of Medicine, School of Medicine, Chiba UniversityJapan
Ryouji Hatano
- First Department of Medicine, School of Medicine, Chiba UniversityJapan
Hiromitsu Saisho
- First Department of Medicine, School of Medicine, Chiba UniversityJapan
Yoshinori Nagato
- First Department of Medicine, School of Medicine, Chiba UniversityJapan
Keiji Suzuki
- Department of Pathology, College of Medical Care and Technology, Gunma UniversityJapan
Katuyuki Nakajima
- Japan Immunoresearch Laboratories Co., GunmaJapan
Masae Yukawa
- National Institute of Radiological Sciences, Chiba,Japan
Fukuo Kondo
- Department of Pathology, School of Medicine, Chiba University, Chiba,Japan
Akihiro Nakayama
- Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan
Hiromu Sakurai
- Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan

Received 27 May 1999; received in revised form 26 January 2000; accepted 1 February 2000.

Abstract

Background/Aim: Accumulation of copper (Cu) in hepatocellular carcinoma (HCC), especially in small tumors, is greater than that in the surrounding liver parenchyma. Metallothionein (MT) is considered to be present as Cu-MT, Zn, Cu-MT or Zn-MT. The aim of this study was to determine the presence and localization of Cu-MT and Zn-MT in HCC and surrounding liver parenchyma.

Methods: In 16 HCC patients, surgically resected specimens including HCC and surrounding liver parenchyma were evaluated.

Results: The level of Cu present in small HCC (<4 cm in diameter) was significantly greater than that in the surrounding liver parenchyma (p<0.05). However, the level of Cu in large HCC (⪢4 cm in diameter) was similar to that in the surrounding liver parenchyma. Analysis by Sephadex G-75 gel filtration revealed that the peak fraction due to Cu was identical to that due to MT in 14 (87.5%) of 16 HCC, the peak fraction due to Cu and Zn was identical to that due to MT in 2 (12.5%) HCC, and the peak fraction due to Zn was identical to that of MT in none of 16 HCC.

Conclusions: Accumulation of Cu in small HCC, in which Cu was present as Cu-MT or Zn, Cu-MT, was greater than that in the surrounding liver parenchyma. Cu accumulation and the presence of MT in the liver may be related to carcinogenesis of HCC, because of the similarity of these findings in the experimental data of Long-Evans rats with a cinnamon-like coat color who develop HCC spontaneously.

Keywords: Carcinogenesis, Copper, Hepatocellular carcinoma (HCC), Metallothionein (MT), Particle-induced X-ray emission (PIXE)