The ability to alter the gap junction protein expression outside GST-P positive foci in liver of rats was associated to the tumour promotion potency of different polychlorinated biphenyls.
The results demonstrate different modes of action by a dioxin-like polychlorinated biphenyl (PCB 126) and a non dioxin-like PCB (PCB 153) in the alteration of connexin (cx) 26 and cx 32 expression outside GST-P positive foci in liver of female Sprague-Dawley rats, treated according to an initiation-promotion protocol. A decreased relative amount of immunopositive cx 26 and cx 32 spots in the parenchymal cell plasma membranes was observed after treatment with the potent tumour promoters PCB 126 or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). No reduction of cx 26 or cx 32 was noted after administration with the weaker tumour promoters PCB 153 or PCB 118 (PCB 118; both dioxin- and non dioxin-like). Additionally, we found that the down-regulation of connexins also occurred in rats treated with PCB 126 or TCDD without partial hepatectomy and initiation with nitrosodiethylamine. In summary, the results indicate that the ability to reduce the gap junction protein level in liver of rats can be associated to the tumour promotive potency of the different PCB-congeners and TCDD.
Bager
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Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Kato
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Y
Kenne
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K
Wärngård
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L
D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D000072259:Connexin 26; D017630:Connexins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097002:Gap Junction beta-1 Protein
D002273:Carcinogens; D000072259:Connexin 26; D017630:Connexins; D005982:Glutathione Transferase; D011078:Polychlorinated Biphenyls; D000072317:Polychlorinated Dibenzodioxins; D000097002:Gap Junction beta-1 Protein; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl