caa a22 4500 445853492 CHVBK 20180317145421.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00204-011-0656-7 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0656-7 Distinct DNA methylation patterns of lysophosphatidic acid receptor genes during rat hepatocarcinogenesis induced by a choline-deficient l -amino acid-defined diet [Elektronische Daten] [Kyoko Okabe, Mai Hayashi, Ikuma Yoshida, Kazuki Nishimura, Nobuyuki Fukushima, Toshifumi Tsujiuchi] Altered expressions of lysophosphatidic acid (LPA) receptor genes have been reported in tumor cells of human and rats. Recently, we detected the frequent mutations of LPA receptor-1 (LPA1) gene in rat hepatocellular carcinomas (HCCs) induced by a choline-deficient l-amino acid-defined (CDAA) diet. In this study, the DNA methylation patterns of LPA receptor genes and their expression levels during rat hepatocarcinogenesis induced by the CDAA diet were investigated. Six-week-old F344 male rats were continuously fed with the CDAA diet, and animals were then killed at 7days and 2, 12, 20, and 75weeks, respectively. Genomic DNAs were extracted from livers and HCCs for the assessment of methylation status by bisulfite sequencing, comparing to normal livers. The livers of rats fed the CDAA diet were unmethylated in LPA1 and LPA2 genes as well as normal livers. In LPA3 gene, although normal livers were unmethylated, the livers at 7days and 2 and 12weeks weakly or moderately methylated and those at 20weeks markedly methylated. Moreover, 4 HCCs were completely methylated in LPA3 gene. Expression levels of LPA receptor genes in the livers of rats fed the CDAA diet and HCCs were correlating with DNA methylation status. These results indicate that DNA methylation status of the LPA3 gene was disturbed in the livers of rats fed the CDAA diet and established HCCs, suggesting that alterations of the LPA receptor genes might be involved during rat hepatocarcinogenesis induced by the CDAA diet. Springer-Verlag, 2011 LPA receptor nationallicence CDAA diet nationallicence Hepatocarcinogenesis nationallicence Methylation nationallicence Rat nationallicence Okabe Kyoko Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut Hayashi Mai Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut Yoshida Ikuma Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut Nishimura Kazuki Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut Fukushima Nobuyuki Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut Tsujiuchi Toshifumi Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut Archives of Toxicology Springer-Verlag 85/10(2011-10-01), 1303-1310 0340-5761 85:10<1303 2011 85 204 https://doi.org/10.1007/s00204-011-0656-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0656-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Okabe Kyoko Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut NATIONALLICENCE 700 1- Hayashi Mai Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut NATIONALLICENCE 700 1- Yoshida Ikuma Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut NATIONALLICENCE 700 1- Nishimura Kazuki Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut NATIONALLICENCE 700 1- Fukushima Nobuyuki Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut NATIONALLICENCE 700 1- Tsujiuchi Toshifumi Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, 577-8502, Osaka, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/10(2011-10-01), 1303-1310 0340-5761 85:10<1303 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer