Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma.
OBJECTIVE
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.
Ebara
M
M
First Department of Medicine, School of Medicine, Chiba University, Japan. ebara@med.m.chiba-u.ac.jp
Fukuda
H
H
Hatano
R
R
Saisho
H
H
Nagato
Y
Y
Suzuki
K
K
Nakajima
K
K
Yukawa
M
M
Kondo
F
F
Nakayama
A
A
Sakurai
H
H
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002850:Chromatography, Gel; D003300:Copper / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D008875:Middle Aged; D013052:Spectrometry, X-Ray Emission; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism*
D003300:Copper; D008668:Metallothionein; D015032:Zinc