PMID- 18174248
OWN - NLM
STAT- MEDLINE
DCOM- 20080325
LR  - 20131121
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 29
IP  - 2
DP  - 2008 Feb
TI  - 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.
PG  - 448-54
LID - 10.1093/carcin/bgm279 [doi]
AB  - 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.
FAU - Kubota, Koji
AU  - Kubota K
AD  - Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, 
      Matsumoto, Nagano 390-8621, Japan.
FAU - Soeda, Junpei
AU  - Soeda J
FAU - Misawa, Ryousuke
AU  - Misawa R
FAU - Mihara, Motohiro
AU  - Mihara M
FAU - Miwa, Shiro
AU  - Miwa S
FAU - Ise, Hirohiko
AU  - Ise H
FAU - Takahashi, Masafumi
AU  - Takahashi M
FAU - Miyagawa, Shinichi
AU  - Miyagawa S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080103
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - N91BDP6H0X (Choline)
RN  - WX1BN24WZT (Ethionine)
SB  - IM
MH  - Animal Feed
MH  - Animals
MH  - Bone Marrow Cells/*metabolism
MH  - Carcinoma, Hepatocellular/*metabolism
MH  - Cell Transformation, Neoplastic
MH  - Choline/*pharmacology
MH  - Ethionine/*pharmacology
MH  - *Gene Expression Regulation, Neoplastic
MH  - Hepatocytes/cytology/*metabolism
MH  - Immunohistochemistry/methods
MH  - Liver/*cytology
MH  - Liver Neoplasms/*metabolism
MH  - Liver Neoplasms, Experimental/metabolism
MH  - Rats
MH  - Rats, Inbred Lew
EDAT- 2008/01/05 09:00
MHDA- 2008/03/26 09:00
CRDT- 2008/01/05 09:00
PHST- 2008/01/05 09:00 [pubmed]
PHST- 2008/03/26 09:00 [medline]
PHST- 2008/01/05 09:00 [entrez]
AID - bgm279 [pii]
AID - 10.1093/carcin/bgm279 [doi]
PST - ppublish
SO  - Carcinogenesis. 2008 Feb;29(2):448-54. doi: 10.1093/carcin/bgm279. Epub 2008 Jan 
      3.