PMID- 8895477
OWN - NLM
STAT- MEDLINE
DCOM- 19961205
LR  - 20231213
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 17
IP  - 10
DP  - 1996 Oct
TI  - Inhibition of gap junctional intercellular communication by barbiturates in 
      long-term primary cultured rat hepatocytes is correlated with liver tumour 
      promoting activity.
PG  - 2119-24
AB  - Rodent liver tumor formation can be promoted by certain barbiturates and this may 
      involve their ability to inhibit hepatocyte gap junctional intercellular 
      communication (GJIC). In order to address the mechanisms and specificity of 
      action of barbiturates on hepatocyte gap junctions, we have compared the effects 
      of liver tumor-promoting barbiturates (phenobarbital, sodium barbital and 
      amobarbital: PB, SB and AB, respectively) and a non-liver tumor-promoting 
      barbiturate (barbituric acid: BA) on primary cultured rat hepatocyte GJIC and 
      connexin32 (Cx32) expression after short (1-24 h) and long (2-14 days) treatment. 
      GJIC was evaluated by fluorescent dye microinjection (dye-coupling); Cx32 
      expression was monitored by Northern blot, Western blot and immunohistochemistry. 
      Both parameters were maintained at high levels over 14 days by coculture of the 
      cells with WB-F344 rat liver epithelial cells in the presence of dexamethasone. 
      Treatment with PB (2 mM) for 1 h sharply reduced dye-coupling from approximately 
      90-30%, but the cells fully recovered by 24 h. No inhibition was seen with the 
      other barbiturates over this 1-day treatment period. Longer treatments (2-14 
      days) with the promoters PB, SB and AB, however, gradually reduced hepatocyte 
      dye-coupling to approximately 30-50%. The non-promoter, BA, did not affect 
      hepatocyte GJIC. These decreases in hepatocyte dye-coupling occurred without 
      changes in Cx32 or gap junction expression. Dye-coupling of WB-F344 cells and 
      expression of their predominant gap junction protein, connexin43 (Cx43), were 
      also not affected. Thus, the inhibition of GJIC was specific to liver tumor 
      promoting barbiturates in hepatocytes, was time-dependent and was not due to 
      altered Cx32 expression.
FAU - Ren, P
AU  - Ren P
AD  - Department of Pathology, Medical College of Ohio, Toledo 43699, USA.
FAU - Ruch, R J
AU  - Ruch RJ
LA  - eng
GR  - CA-57612/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Barbiturates)
RN  - 0 (Carcinogens)
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Barbiturates/*pharmacology
MH  - *Carcinogens
MH  - Cell Communication/*drug effects
MH  - Cells, Cultured
MH  - Connexin 43/metabolism
MH  - Connexins/metabolism
MH  - Gap Junctions/*physiology
MH  - Gene Expression
MH  - Liver/cytology
MH  - Liver Neoplasms/chemically induced
MH  - Male
MH  - Rats
MH  - Rats, Inbred F344
MH  - Gap Junction beta-1 Protein
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
AID - 10.1093/carcin/17.10.2119 [doi]
PST - ppublish
SO  - Carcinogenesis. 1996 Oct;17(10):2119-24. doi: 10.1093/carcin/17.10.2119.