Abstract
Many hydrocarbons are environmental pollutants that, due to their iipophiiicity 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.
Keywords
- Intercellular Communication
- Organochlorine Compound
- Relative Band Intensity
- Altered Hepatic Focus
- Liver Derive Cell Line
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
Bager Y, Kenne K, Krutovskikh V, Mesnil M, Traub O, Wärngard L (1994) Alteration in expression of gap junction proteins in rat liver after treatment with the tumour promoter 3,4,5,3’,4’-Pentachlorobiphenyl. Carcinogenesis 15:2439–2443
Birtley RDN, Conning DM, Daniel JW, Ferguson DM, Longstaff E, Swan AAB (1980) The toxicological effects of chlorinated paraffins in mammals. Toxicol Appl Pharmacol 54:514–525
Bucher JR, Alison RH, Montgomery CA, Huff J, Haseman JK, Farnell D, Thompson R, Prejean JD (1987) Comparative toxicity and carcinogenicity of two chlorinated paraffins in F344/N rats and B6C3F1 mice. Fund Appl Toxicol 9:454–468
Dermietzel R, Traub O, Hwang TK, Beyer E, Bennett MVL, Spray DC, Willecke K (1989) Differential expression of three gap junction proteins in developing and mature brain tissues. Proc Natl Acad Sci, USA 86:10148–10152
El-Fouly MH, Trosko JE, Chang CC (1987) Scrape-loading and dye transfer. A rapid and simple technique to study gap junctional intercellular communication. Exp Cell Res 168:422–430
Fransson-Steen R, Flodström S, Wärng7#x00E1;rd L (1992) The insecticide endosulfan and its two stereoisomers promote the growth of altered hepatic foci in rats. Carcinogenesis 13:2299–2303
Hemming H, Wärngard L, Ahlborg UG (1991) Inhibition of dye transfer in rat liver WB cell culture by polychlorinated biphenyls. Pharm Tox 69:416–420
Kenne K, Fransson-Steen R, Honkasalo S, Warngard L (1994) Two inhibitors of gap junctional intercellular communication, TPA and endosulfan: Different effects on phosphorylation of connexin 43 in the rat liver epithelial ceil line, IAR 20. Carcinogenesis 15:1161–1165
Musil LS, Goodenough DA (1993) Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin 43, occurs after exit from the ER. Cell 74:1065–1077
Nicholson B, Dermietzel R, Teplow D, Traub O, Willecke K, Revel JP (1987) Two homologous protein component of hepatic gap junctions. Nature 329:732–734
NTP (National Toxicology Program) (1986a) Toxicology and carcinogenesis studies of chlorinated paraffins (CI2,60% chlorine) (CAS NO. 63449-39-8) in F344/N rats and B6C3F1 mice (gavage studies). NTP-TR-308. (Technical report series). Research Triangle Park, NC
NTP (National Toxicology Program) (1986b) Toxicology and carcinogenesis studies of chlorinated paraffins (C23,43% chlorine) (CAS NO. 63449-39-8) in F344/N rats and B6C3F1 mice (gavage studies). NTP-TR-305. Technical Report Series. Research Triangle Park, NC
Poland A (1991) Receptor-mediated toxicity: Reflections on a quantitative model for risk assessment In: Biological basis for risk assessment of dioxins and related compounds. Banbury Report 35, Cold Spring Harbor Laboratory Press, pp 417–426
Ruch RJ, Fransson R, Flodström S, Wärngard L, Klaunig JE (1990) Inhibition of hepatocyte gap junctional intercellular communication by endosulfan, chlordane and heptachlor. Carcinogenesis 11:1097–1101
Serrone DM, Birtley RDN, Weigand W, Millischer R (1987) Toxicology of chlorinated paraffins. Food Chem Toxicol 25:553–562
Willecke K, Hennemann H, Dahl E, Jungbluth S, Heynkes R (1991) The diversity of connexin genes encoding gap junctional proteins. Eur J Cell Biol 56:1–7
Wärngárd L, Hemming H, Flodström S, Duddy S and Kass G (1989) Mechanistical studies on DDT-induced inhibition of intercellular communication. Carcinogenesis 10:471–476
Wärngard L, Flodström S (1989) Mechanistical studies on TPA-, pyrethroid- and DDT- induced effects in the V79 metabolic cooperation assay. Ceil Biol Toxicol 5:67–75
Wärngárd L, Bager Y, Hemming H, Honkasalo S, Kenne K (1994) The effect of 3,4,5,3’,4-Pentachlorophenyl and 2,3,7,8-Tetrachlorodibenzo-p-dioxin on gap junctional intercellular communication in vitro and in vivo. Progress in Cell Research 4:119–122
Yamasaki H, (1990) Gap junctional intercellular communication and carcinogenesis. Carcinogenesis 11:1051–1058
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© 1996 Springer-Verlag Berlin Heidelberg
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Wärngard, L., Bager, Y., Kato, Y., Kenne, K., Ahlborg, U.G. (1996). Mechanistical studies of the inhibition of intercellular communication by organochlorine compounds. In: Seiler, J.P., Kroftová, O., Eybl, V. (eds) Toxicology - From Cells to Man. Archives of Toxicology, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61105-6_16
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DOI: https://doi.org/10.1007/978-3-642-61105-6_16
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