title: Development of hepatocellular adenomas and carcinomas associated with fibrosis in C57BL/6J male mice given a choline-deficient, L-amino acid-defined diet.
abstract: 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.
authors.affiliation: Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Nara 634-8521, Japan. adenda@nmu-gw.cc.naramed-u.ac.jp
authors.forename: Ayumi
authors.initials: A
authors.lastname: Denda
authors.forename: Wakashi
authors.initials: W
authors.lastname: Kitayama
authors.forename: Hideki
authors.initials: H
authors.lastname: Kishida
authors.forename: Nao
authors.initials: N
authors.lastname: Murata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
authors.forename: Dai
authors.initials: D
authors.lastname: Nakae
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000236:Adenoma / Q000209:etiology*; D000596:Amino Acids / Q000172:deficiency*; D000818:Animals; D002277:Carcinoma / Q000209:etiology*; D002796:Choline Deficiency / Q000150:complications*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D008106:Liver Cirrhosis, Experimental / Q000209:etiology*; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000596:Amino Acids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine