PMID- 8968061
OWN - NLM
STAT- MEDLINE
DCOM- 19970127
LR  - 20231213
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 17
IP  - 11
DP  - 1996 Nov
TI  - Decreased connexin32 and a characteristic enzyme phenotype in clofibrate-induced 
      preneoplastic lesions not shared with spontaneously occurring lesions in the rat 
      liver.
PG  - 2441-8
AB  - Two different types of focal preneoplastic lesions, tentatively named Type I and 
      II lesions, were recognized in the liver of rats chronically treated with 
      clofibrate for 104 weeks. Type I lesions were characterized by mostly negative 
      glucose-6-phosphate dehydrogenase (G6PD) activity (6 out of 10, 60%) and positive 
      expression of succinate dehydrogenase (10 out of 10, 100%), in addition to the 
      previously documented complete lack of expression of glutathione S-transferase, 
      placental form (GST-P) and gamma-glutamyl transpeptidase (GGT). Furthermore, most 
      importantly, Type I lesions exhibited a clear decrease in immunohistochemically 
      demonstrated connexin32 (Cx32) spot counts on their hepatocyte membranes, 
      similarly to nitrosamine-induced lesions. In contrast, Type II lesions, mostly 
      small in size and positively expressing GST-P and/or GGT and G6PD, similarly to 
      their previously reported nitrosamine-induced counterparts, did not exhibit a 
      significant decrease in Cx32 count. In addition, spontaneously occurring lesions, 
      again sharing the same enzyme phenotype, did not show a decrease in Cx32. The 
      results indicate that: (i) a clear distinction between the two lesions, with Type 
      I being involved in clofibrate-induced tumors and Type II being more likely to be 
      spontaneous in nature; (ii) a decrease in Cx32 is closely linked to lesion 
      development and possibly stage of progression, irrespective of the enzyme 
      phenotype and the applied carcinogen; (iii) the unaltered condition of Cx32 may 
      suggest a slow growing or non-progressive nature.
FAU - Tsuda, H
AU  - Tsuda H
AD  - Chemotherapy Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, 
      Japan.
FAU - Asamoto, M
AU  - Asamoto M
FAU - Iwahori, Y
AU  - Iwahori Y
FAU - Hori, T
AU  - Hori T
FAU - Ota, T
AU  - Ota T
FAU - Baba-Toriyama, H
AU  - Baba-Toriyama H
FAU - Uehara, N
AU  - Uehara N
FAU - Kim, D J
AU  - Kim DJ
FAU - Krutovskikh, V A
AU  - Krutovskikh VA
FAU - Takasuka, N
AU  - Takasuka N
FAU - Tsuchiya, T
AU  - Tsuchiya T
FAU - Mutai, M
AU  - Mutai M
FAU - Tatematsu, M
AU  - Tatematsu M
FAU - Yamasaki, H
AU  - Yamasaki H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Carcinogens)
RN  - 0 (Connexins)
RN  - 13147-25-6 (N-ethyl-N-hydroxyethylnitrosamine)
RN  - 3IQ78TTX1A (Diethylnitrosamine)
RN  - EC 2.3.2.2 (gamma-Glutamyltransferase)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - HPN91K7FU3 (Clofibrate)
SB  - IM
MH  - Animals
MH  - Carcinogens/*toxicity
MH  - Clofibrate/*toxicity
MH  - Connexins/*metabolism
MH  - Diethylnitrosamine/analogs & derivatives/toxicity
MH  - Glutathione Transferase/metabolism
MH  - Liver Neoplasms, Experimental/*chemically induced/*enzymology/metabolism
MH  - Male
MH  - Microbodies/drug effects
MH  - Phenotype
MH  - Precancerous Conditions/*chemically induced/*enzymology/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - gamma-Glutamyltransferase/metabolism
MH  - Gap Junction beta-1 Protein
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
AID - 10.1093/carcin/17.11.2441 [doi]
PST - ppublish
SO  - Carcinogenesis. 1996 Nov;17(11):2441-8. doi: 10.1093/carcin/17.11.2441.