Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model

Koji Kubota, Junpei Soeda, Ryousuke Misawa, Motohiro Mihara, Shiro Miwa, Hirohiko Ise, Masafumi Takahashi, Shinichi Miyagawa

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Abstract

Bone marrow cells (BMCs) have been reported to behave as tissue-specific stem cells in some organs and to participate in tumorigenesis. However, the roles of BMCs in hepatic regeneration and carcinogenesis are still unknown. A choline-deficient, ethionine-supplemented (CDE) diet leads to the appearance of oval cells, a type of hepatic progenitor cell, and activates their replication. Furthermore, this type of diet induces preneoplastic nodules and hepatocellular carcinomas (HCCs) derived from oval cell progenitors. The aims of this study were to determine whether oval cells are derived from BMCs and whether preneoplastic nodules or HCCs originate from BMCs in the CDE diet rat model. To clarify the origin of constituent cells in the liver, we transplanted BMCs from green fluorescent protein (GFP) transgenic female rats into male Lewis rats, which were then exposed to a CDE diet to induce hepatocarcinogenesis. Some oval cells showed both donor-derived GFP expression and the recipient-specific Y chromosome, indicating that donor BMCs fused with recipient oval cells. Several preneoplastic nodules (precancerous lesions) identified by their glutathione S-transferase placental (GSTp) positivity were induced by CDE treatment. However, these preneoplastic GSTp-positive nodules were not GFP positive. In conclusion, this study has produced two major findings. First, BMCs fuse with some oval cells. Second, BMC-fused oval cells and BMCs might not have malignant potential in the CDE-treated rat model.

Original languageEnglish
Pages (from-to)448-454
Number of pages7
JournalCarcinogenesis
Volume29
Issue number2
DOIs
Publication statusPublished - Feb 1 2008

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Ethionine
Choline
Bone Marrow Cells
Hepatocytes
Carcinogenesis
Diet
Liver
Green Fluorescent Proteins
Stem Cells
Glutathione Transferase
Hepatocellular Carcinoma
Transgenic Rats
Y Chromosome
Regeneration

All Science Journal Classification (ASJC) codes

  • Cancer Research

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Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model. / Kubota, Koji; Soeda, Junpei; Misawa, Ryousuke; Mihara, Motohiro; Miwa, Shiro; Ise, Hirohiko; Takahashi, Masafumi; Miyagawa, Shinichi.

In: Carcinogenesis, Vol. 29, No. 2, 01.02.2008, p. 448-454.

Research output: Contribution to journalArticle

Kubota, Koji ; Soeda, Junpei ; Misawa, Ryousuke ; Mihara, Motohiro ; Miwa, Shiro ; Ise, Hirohiko ; Takahashi, Masafumi ; Miyagawa, Shinichi. / Bone marrow-derived cells fuse with hepatic oval cells but are not involved in hepatic tumorigenesis in the choline-deficient ethionine-supplemented diet rat model. In: Carcinogenesis. 2008 ; Vol. 29, No. 2. pp. 448-454.
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