Biomaterial Database

Inhibition of gap junctional intercellular communication by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat hepatocytes. 1995

T K Baker, and A P Kwiatkowski, and B V Madhukar, and J E Klaunig

Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202-5196, USA.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent rodent hepatic tumor promoter. Unlike observations with the majority of tumor promoting chemicals studied to date, most investigations have failed to demonstrate down-regulation of gap junctional intercellular communication (GJIC) in cultured cells by TCDD. The present study examined the effect of TCDD on GJIC in rat hepatocytes in primary culture. At non-cytolethal doses TCDD inhibited GJIC in a time- (1, 4, 24 and 48 h) and concentration (1 x 10(-8) - 1 x 10(-14) M)-dependent manner. This inhibition occurred within 4 h of treatment at doses of 1 x 10(-8) - 1 x 10(-12) M TCDD and persisted for up to 48 h, despite removal of TCDD. Treatment of rat hepatocytes with TCDD resulted in a decrease in hepatocyte connexin 32 mRNA, but had no apparent effect on connexin 26 mRNA. Co-incubation of rat hepatocytes with TCDD and alpha-napthoflavone abolished down-regulation of GJIC by TCDD. Similarly, co-treatment with a cAMP analog (8-bromoadenosine 3',5'-cyclic monophosphate) prevented down-regulation of GJIC by TCDD. The results of this investigation demonstrated, for the first time, that TCDD inhibits GJIC in the in vivo target of its tumor promoting effect and that this effect may, in part, be mediated through the Ah receptor. In addition, this study showed that inhibition of GJIC by TCDD may be due to transcriptional down-regulation or stability of the connexin 32 gap junction mRNA.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D011916	Rats, Inbred F344	An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes.	Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002273	Carcinogens	Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.	Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002450	Cell Communication	Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.	Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D000072317	Polychlorinated Dibenzodioxins	Dibenzodioxin derivatives that contain multiple chloride atoms bound to the benzene ring structures.	TCDD,Tetrachlorodibenzodioxin,2,3,7,8-Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo-p-dioxins,Dibenzo(b,e)(1,4)dioxin, 2,3,7,8-tetrachloro-,PCDD,Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzodioxin,Polychlorodibenzo-4-dioxin,Polychlorodibenzo-p-dioxin,Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo p dioxins,Dibenzo-p-dioxins, Chlorinated,Dibenzo-p-dioxins, Polychlorinated,Dibenzodioxin, Polychlorinated,Dibenzodioxins, Polychlorinated,Polychlorinated Dibenzo p dioxins,Polychlorodibenzo 4 dioxin,Polychlorodibenzo p dioxin,Tetrachlorodibenzo p dioxin
D000097002	Gap Junction beta-1 Protein	A GAP JUNCTION beta subunit containing four transmembrane domains expressed in myelinating SCHWANN CELLS and is localized to peripheral MYELIN (e.g., noncompact myelin in the paranode and Schmitt-Lanterman incisures). Mutations in the human gene GJB1 are associated with X-linked CHARCOT-MARIE-TOOTH DISEASE type 1 (CMT1X).	Connexin 32,Connexin 32 Protein,Cx32 Protein,GJB1 Protein,Gap Junction B1,Gap Junction beta1 Protein,Gap Junction beta 1 Protein,Protein, Connexin 32,Protein, Cx32,Protein, GJB1
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia