title: Disturbance of DNA methylation patterns in the early phase of hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined diet in rats.
abstract: The authors investigated the DNA methylation patterns of the E-cadherin, Connexin 26 (Cx26), Rassf1a and c-fos genes in the early phase of rat hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined (CDAA) diet. Six-week-old F344 male rats were continuously fed with the CDAA diet, and three animals were then killed at each of 4 and 8 days and 3 weeks. Genomic DNA was extracted from livers for assessment of methylation status in the 5' upstream regions of E-cadherin, Cx26, Rassf1a and c-fos genes by bisulfite sequencing, compared with normal livers. The livers of rats fed the CDAA diet for 4 and 8 days and 3 weeks were methylated in E-cadherin, Cx26 and Rassf1a genes, while normal livers were all unmethylated. In contrast, normal livers were highly methylated in c-fos gene. Although the livers at 4 days were weakly methylated, those at 8 days and 3 weeks were markedly unmethylated. Methylation patterns of CpG sites in E-cadherin, Cx26 and Rassf1a were sparse and the methylation was not associated with gene repression. These results indicate that gene-specific DNA methylation patterns were found in livers of rats after short-term feeding of the CDAA diet, suggesting gene-specific hypermethylation might be involved in the early phase of rat hepatocarcinogenesis induced by the CDAA diet.
authors.affiliation: Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Mariko
authors.initials: M
authors.lastname: Onishi
authors.forename: Eriko
authors.initials: E
authors.lastname: Sugata
authors.forename: Yui
authors.initials: Y
authors.lastname: Sokuza
authors.forename: Chiharu
authors.initials: C
authors.lastname: Mori
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D002796:Choline Deficiency / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation; D004032:Diet / Q000009:adverse effects*; D015972:Gene Expression Regulation, Neoplastic; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000596:Amino Acids; D015820:Cadherins; D017630:Connexins; C000607044:Gjb2 protein, rat; D016760:Proto-Oncogene Proteins c-fos; D025521:Tumor Suppressor Proteins; D000072259:Connexin 26; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases