Immunohistochemical demonstration of the gap junctional protein connexin 32 and proliferating cell nuclear antigen in glutathione S-transferase placental form-negative lesions of rat liver induced by diethylnitrosamine and clofibrate.
The distributions of a gap junctional protein, connexin 32 (cx 32), and proliferating cell nuclear antigen (PCNA) were examined immunohistochemically in glutathione S-transferase placental form (GST-P)-negative foci, induced in rat liver by initiation with diethylnitrosamine (DEN, 200 mg/kg) followed by promotion with clofibrate (1% in diet) in an in vivo medium-term assay system for hepatocarcinogenesis. The results were compared to those in GST-P-positive foci induced by DEN alone. The treatment with clofibrate caused the appearance of GST-P-negative foci, increased in size as compared to GST-P-positive foci in the same liver or induced by the DEN alone. The proportion of PCNA-positive hepatocytes in GST-P-negative foci was significantly higher than in the surrounding parenchyma, indicating increased cell proliferation. The numbers of cx 32-positive spots per hepatocyte in GST-P-negative foci were clearly decreased, reaching 65.4% at week 20 and 51.8% at week 30 of values for surrounding normal hepatocytes. In GST-P-positive foci induced by DEN, only a slight decrease (80%) was observed at week 8. These findings show that a positive association between the sustained inhibition of gap junctional intercellular communication and increased cell proliferation of GST-P-negative foci in Fischer-344 male rats induced with DEN and promoted with clofibrate.
Ito
S
S
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Tateno
C
C
Tuda
M
M
Yoshitake
A
A
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002994:Clofibrate / Q000633:toxicity*; D017630:Connexins / Q000032:analysis*; D004052:Diethylnitrosamine / Q000633:toxicity*; D004357:Drug Synergism; D005982:Glutathione Transferase / Q000032:analysis*; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry* / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000737:chemistry* / Q000201:enzymology*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D000097002:Gap Junction beta-1 Protein
D002273:Carcinogens; D002994:Clofibrate; D017630:Connexins; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D018809:Proliferating Cell Nuclear Antigen; D000097002:Gap Junction beta-1 Protein