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Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats
Author(s) -
Sone Hideko,
Maeda Mitsuaki,
Gotoh Masahiro,
Wakabayashi Keiji,
Ono Takao,
Yoshida Michihiro C.,
Takeichi Noritoshi,
Mori Michio,
Hirohashi Setsuo,
Sugimura Takashi,
Nagao Minako
Publication year - 1992
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940050306
Subject(s) - hepatitis , ceruloplasmin , biology , copper , acute hepatitis , medicine , endocrinology , immunology , chemistry , organic chemistry
The concentration of copper in the livers of Long‐Evans rats with cinnamon‐like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F 1 backcrosses (LEC F 1 × LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F 1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long‐Evans with agouti coat color or Brown‐Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene. © 1992 Wiley‐Liss, Inc.