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Journal of Histochemistry and Cytochemistry, Vol. 50, 1263-1271, September 2002, Copyright © 2002, The Histochemical Society, Inc.

ARTICLE

Localization of the Induced Metallothionein and DNA Damage in Rat Kidney After Gold Injection

Shigeru Saitoa, Masaaki Kurasakib, Toshiyuki Hosokawac, Masashi Okabeb, Takeshi Saitod, Yukiko Fujiie, Kazuo Nagashimae, and Katsumi Yoshidaa
a Department of Preventive Medicine, St Marianna University School of Medicine, Kawasaki, Japan
b Department of Environmental Medicine and Informatics, Graduate School of Environmental Earth Science, Hokkaido University, Sapporo, Japan
c Research Division for Higher Education, Center for Research and Development in Higher Education, Hokkaido University, Sapporo, Japan
d Laboratory of Environmental Biology, Hokkaido University School of Medicine, Sapporo, Japan
e Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan

Correspondence to: Shigeru Saito, Dept. of Preventive Medicine, St Marianna University School of Medicine, Kawasaki 216-8511, Japan.

To clarify the relationships between DNA damage and Cu-MT and between DNA damage and Cu in kidneys of rats injected with Au, we examined the histochemical localization of DNA damage, metallothionein (MT), and the accumulated Cu in the kidneys of rats injected with Au, Cu, or Cu-MT. The immunoreactivity of MT was observed predominantly in the outer stripe of the outer medulla and the inner cortex of the Au-injected rat, and the signals of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) were observed in the cortex. Cu detected by Timm's method was mainly distributed in the cortex of the Au-injected rat. These results indicated that DNA damage could be caused by free Cu in the cortex but not by the Cu bound to MT in the outer stripe of the outer medulla. This consideration was supported by the data from rats injected with Cu and Cu-MT. Furthermore, we determined the Cu contents in three fractions (cytosol, organelle, and precipitate-containing nuclei) of the kidneys. Interestingly, most of the Cu content in the kidney of the rat injected with Au or Cu-MT was detected in the cytosol, whereas most of the Cu content in the kidney of the rat injected with Cu was detected in the nuclei-containing precipitate. These findings suggest that the DNA damage in the kidneys of rats injected with Au may be associated with Cu-binding proteins but not with Cu-MT. (J Histochem Cytochem 50:1263–1271, 2002)

Key Words: gold, copper, Cu-MT, kidney, TUNEL, metallothionein, DNA damage


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