PMID- 1310907
OWN - NLM
STAT- MEDLINE
DCOM- 19920323
LR  - 20190509
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 13
IP  - 2
DP  - 1992 Feb
TI  - Persistence of the cholangiocellular and hepatocellular lesions observed in rats 
      fed a choline-deficient/DL-ethionine-supplemented diet.
PG  - 271-6
AB  - Male outbred Sprague-Dawley rats were fed a choline-deficient diet containing 
      0.10% DL-ethionine (CDE) for 4, 6, 10, 14 or 22 weeks followed by a standard diet 
      for up to 59 weeks. Liver sections were histochemically analyzed for the 
      following parameters: basophilia, glycogen content and the activities of glycogen 
      synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6PASE), 
      glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate 
      dehydrogenase (GAPDH), glycerin-3-phosphate dehydrogenase (G3PDH), 'malic enzyme' 
      (MDH), alkaline phosphatase (ALKPASE) and gamma-glutamyltranspeptidase (GGT). The 
      stop experiments revealed that many of the oval cells proliferating during the 
      first 4-6 weeks may undergo necrotic changes and disappear with time, whereas 
      cholangiofibroses appearing in animals fed CDE for at least 10 weeks are 
      persistent lesions. The sequence of lesions seen in this study, leading from 
      persistent oval cells through cholangiofibroses to cholangiofibromas, strongly 
      suggests that the oval cells are the precursor cells of cholangiocellular tumors. 
      The proliferating oval cells and the hepatic foci consisting of clear and 
      acidophilic or mixed cell populations were always spatially separated and no 
      transitions between oval and parenchymal cells were observed. These results argue 
      against a precursor-product relationship between oval and parenchymal cells. Both 
      proliferating and persistent oval cells, cholangiofibroses and cholangiofibromas 
      showed a strong staining for G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT; low PHO, 
      SYN and G6PASE activities were also detected in these lesions. Persistent 
      glycogen-storage foci, which developed in all rats fed CDE for 4-14 weeks 
      followed by a normal lab chow for over a year, had increased PHO, G6PDH, MDH, 
      ALKPASE and GGT activities, while SYN, GAPDH and G3PDH activities remained 
      unaltered and G6PASE activity decreased. Mixed cell foci appearing in animals fed 
      CDE for 22 weeks followed by a normal lab chow for 59 weeks had strongly 
      increased G6PDH, GAPDH, G3PDH, MDH, ALKPASE and GGT activities as well as 
      decreased G6PASE activity. These results indicate that the characteristic 
      metabolic pattern of preneoplastic hepatic foci is independent of the further 
      administration of the carcinogenic diet. The shift from glycogen metabolism to 
      glycolysis and the pentose phosphate pathway occurring during the later stages of 
      CDE-induced hepatocarcinogenesis is an autogenous process apparently directing 
      the disturbed carbohydrate metabolism towards alternative metabolic pathways. A 
      similar metabolic shift also seems to take place during cholangiocarcinogenesis.
FAU - Hacker, H J
AU  - Hacker HJ
AD  - Division of Cytopathology, German Cancer Research Center, Heidelberg.
FAU - Steinberg, P
AU  - Steinberg P
FAU - Toshkov, I
AU  - Toshkov I
FAU - Oesch, F
AU  - Oesch F
FAU - Bannasch, P
AU  - Bannasch P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - EC 1.- (Oxidoreductases)
RN  - EC 2.- (Transferases)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - N91BDP6H0X (Choline)
RN  - WX1BN24WZT (Ethionine)
SB  - IM
MH  - Adenoma, Bile Duct/enzymology/*pathology
MH  - Animals
MH  - Bile Duct Neoplasms/enzymology/*pathology
MH  - Choline/*administration & dosage/toxicity
MH  - Ethionine/*administration & dosage
MH  - Immunoenzyme Techniques
MH  - Liver Neoplasms, Experimental/enzymology/*pathology
MH  - Male
MH  - Oxidoreductases/metabolism
MH  - Phosphoric Monoester Hydrolases/metabolism
MH  - Rats
MH  - Transferases/metabolism
EDAT- 1992/02/01 00:00
MHDA- 1992/02/01 00:01
CRDT- 1992/02/01 00:00
PHST- 1992/02/01 00:00 [pubmed]
PHST- 1992/02/01 00:01 [medline]
PHST- 1992/02/01 00:00 [entrez]
AID - 10.1093/carcin/13.2.271 [doi]
PST - ppublish
SO  - Carcinogenesis. 1992 Feb;13(2):271-6. doi: 10.1093/carcin/13.2.271.