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2002 ; 93
(2
): 125-32
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Development of hepatocellular adenomas and carcinomas associated with fibrosis in
C57BL/6J male mice given a choline-deficient, L-amino acid-defined diet
#MMPMID11856475
Denda A
; Kitayama W
; Kishida H
; Murata N
; Tsutsumi M
; Tsujiuchi T
; Nakae D
; Konishi Y
Jpn J Cancer Res
2002[Feb]; 93
(2
): 125-32
PMID11856475
show ga
Development of hepatocellular carcinomas in rats caused by a choline-deficient,
L-amino acid-defined (CDAA) diet, usually associated with fatty liver, fibrosis,
cirrhosis and oxidative DNA damage, has been recognized as a useful model of
hepatocarcinogenesis caused by endogenous factors. In the present study, in order
to further explore involved factors and genes, we established an equivalent model
in spontaneous liver tumor-resistant C57BL/6J mice. Six-week-old males and
females were continuously fed the CDAA diet and histological liver lesions and
oxidative DNA damage due to 8-hydroxydeoxyguanosine (8-OHdG) were examined after
22, 65 and 84 weeks. In male mice, fatty change and fibrosis were evident at 22
weeks, and preneoplastic foci of altered hepatocytes were seen at an incidence of
8/8 (100%) and a multiplicity of 6.6 +/- 4.0 per mouse at 65 weeks.
Hepatocellular adenomas and carcinomas developed at incidences of 16/24 (66.7%)
and 5/24 (20.8%), and multiplicities of 1.42 +/- 1.32 and 0.29 +/- 0.62,
respectively, at 84 weeks. The female mice exhibited resistance to development of
these lesions. The CDAA diet also increased 8-OHdG levels in male but not female
mice. These results indicate that a CDAA diet causes hepatocellular preneoplastic
foci, adenomas and carcinomas associated with fibrosis and oxidative DNA damage
in mice, as in rats, providing a hepatocarcinogenesis model caused by endogenous
factors in mice.