Development of hepatocellular adenomas and carcinomas associated with fibrosis in C57BL/6J male mice given a choline-deficient, L-amino acid-defined diet.
Development of hepatocellular adenomas and carcinomas associated with fibrosis in C57BL/6J male mice given a choline-deficient, L-amino acid-defined diet.
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DOI：
10.1111/j.1349-7006.2002.tb01250.x
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发表时间：
2002-03
期刊：
影响因子：
--
通讯作者：
Konishi Y
中科院分区：
文献类型：
--
作者：
Denda A;Kitayama W;Kishida H;Murata N;Tsutsumi M;Tsujiuchi T;Nakae D;Konishi Y
由胆碱缺乏、L-氨基酸限定（CDAA）饮食引起的大鼠肝细胞癌的发生通常与脂肪肝、纤维化、肝硬化和氧化性DNA损伤相关，已被认为是内源性因素引起的肝癌发生的有用模型。为了进一步探讨肝癌的相关因素和基因，本研究建立了一种自发性肝癌耐药C57 BL/6 J小鼠的等效模型。6周龄雄性和雌性动物连续喂食CDAA饲料，并在22、65和84周后检查了组织学肝脏病变和8-羟基脱氧鸟苷（8-OHdG）引起的氧化性DNA损伤。在雄性小鼠中，脂肪变化和纤维化在22周时明显，并且在65周时观察到改变的肝细胞的癌前病灶，发生率为8/8（100%），多重性为6.6±4.0/小鼠。84周时，肝细胞腺瘤和癌的发生率分别为16/24（66.7%）和5/ 24（20.8%），多重性分别为1.421±1.32和0.29±0.62。雌性小鼠表现出对这些病变发展的抵抗力。CDAA饲料还增加了雄性小鼠而非雌性小鼠的8-OHdG水平。这些结果表明，CDAA饮食在小鼠中引起与纤维化和氧化DNA损伤相关的肝细胞癌前病变、腺瘤和癌，如在大鼠中一样，提供了由内源性因素引起的小鼠肝癌发生模型。
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 1.421±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.
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DOI：
10.1016/s0005-2760(97)00011-8
发表时间：
1997-05-17
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
Houweling, M;Cui, Z;Vance, DE
通讯作者：
Vance, DE
影响因子：
1.5
作者：
Latendresse, JR;Pereira, MA
通讯作者：
Pereira, MA
影响因子：
1.5
作者：
Moser, GJ;Wolf, DC;Goldsworthy, TL
通讯作者：
Goldsworthy, TL
影响因子：
1.5
作者：
Newberne, Paul M;Camargo, Joao Lauro V de;Clark, Anthony J
通讯作者：
Clark, Anthony J
影响因子：
4.7
作者：
Denda, A;Endoh, T;Konishi, Y
通讯作者：
Konishi, Y