Mechanistical studies of the inhibition of intercellular communication by organochlorine compounds.
Many hydrocarbons are environmental pollutants that, due to their lipophilicity and chemical stability, accumulate in biological systems including milk and body fat. A number of investigations have demonstrated that many organochlorine compounds can act as tumour promoters in vivo and inhibit gap junctional intercellular communication between cells in culture. In the present study we have investigated the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), different polychlorinated biphenyls, chlorinated paraffins and the pesticide endosulfan. Using techniques of scrape loading dye/transfer and Western blot analysis the function, expression and phosphorylation of different connexins in vitro and in vivo were studied. The results show a good correlation between the ability to act as a tumour promoter and to interfere with gap junctional intercellular communication. All tested compounds inhibited the intercellular communication in a liver derived cell line (IAR 20). However, the results show that the time to inhibition varies between the different agents. Endosulfan and chlorinated paraffins inhibit the communication within one hour, whereas dioxin like substances need to expose the cells for 48 hours before the communication is affected.
Wärngárd
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L
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Bager
Y
Y
Kato
Y
Y
Kenne
K
K
Ahlborg
U G
UG
D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D004726:Endosulfan / Q000633:toxicity*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000166:cytology; D010232:Paraffin / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship
D007306:Insecticides; D000072317:Polychlorinated Dibenzodioxins; D010232:Paraffin; D011078:Polychlorinated Biphenyls; D004726:Endosulfan