Gap junctional intercellular communication

Fransson-Steen R, Warngard L. 1992. Inhibitory effects of endosulfan on gap junctional intercellular communication in WB-F344 rat liver cells and primary rat hepatocytes. Carcinogenesis 13(4) 657-662. 

Kenne K, Fransson-Steen R, Honkasalo S, et al. 1994. Two inhibitors of gap junctional intercellular communication, TPA and endosulfan Different effects on phosphorylation of connexin 43 in the rat liver epithelial cell line, lAR 20. Carcinogenesis 15(6) 1161-1165. 

Another study showed that a mixture of oxidative metabolites of P-carotene, but not P-carotene, was able to increase the binding of benzo[a]pyrene to DNA. Other mixtures of P-carotene cleavage products have been shown to induce oxidative stress in vitro,exert cytotoxic and genotoxic effects, and inhibit gap junction intercellular communications. It has been suggested that these detrimental effects could possibly occur in vivo following the intake of high doses of carotenoids. 

Yeh, S.L. and Hu, M.L., Oxidized [beta]-carotene inhibits gap junction intercellular communication in the human lung adenocarcinoma cell line A549, Food Chem. Toxicol., 41, 1677, 2003. 

Trosko, J. E., C. C. Chang, B. Upham, and M. Wilson. 1998. Epigenetic toxicology as toxicant-induced changes in intracellular signalling leading to altered gap junctional intercellular communication. Toxicol Lett 102-103 71-78. 

Heptachlor, chlordane, and endosulfan (another cyclodiene pesticide) were shown to inhibit hepatocyte gap junctional intercellular communication (Ruch et al. 1990). All three pesticides showed similar dose-response relationships. Further testing with chlordane and heptachlor indicated that inhibition of the cytochrome P-450 system had no effect on this response. These results suggest that the interference with intercellular communication is not directly tied into the effects of these cyclodienes on the P-450 system. 

Ruch RJ, Fransson R, Flodstrom S, etal. 1990. Inhibition of hepatocyte gap junctional intercellular communication by endosulfan, chlordane, and heptachlor. Carcinogenesis 11 (7) 1097-1102. 

Morton, and D. ]. Doolittle. Gap junction intercellular communication and cytotoxicity in normal human cells after exposure to smoke condensates from cigarettes that burn or primarily heat tobacco. Toxicol In Vitro 2000 14(1) 41-51. 

Inhibition of gap-junetional intercellular communieation, Chinese hamster V79 eells in vitro Inhibition of gap-junctional intercellular communication, Chinese hamster V79 cells in vitro Inhibition of gap-junctional intercellular communication, Syrian hamster embryo cells in vitro Inhibition of gap-junctional intercellular communication, Chinese hamster V79 cells in vitro Inhibition of gap-junctional intercellular communication, Chinese hamster V79 cells and Syrian hamster embryo cells in vitro... 

RLV/Fischer rat assay without the addition of an exogenous metabolic activation system. In a single study, mouse JB6 epidermal cells were transformed by di(2-ethyl-hexyl) phthalate without activation and in one of two studies a weak response was reported in the CSHIOT A cell transformation assay with di(2-ethylhexyl) phthalate in either the absence or presence of exogenous metabolic activation. BALB/c-3T3 cells were not transformed by di(2-ethylhexyl) phthalate with or without metabolic activation. Di(2-ethylhexyl) phthalate inhibited gap-junctional intercellular communication in Chinese hamster V79 cells in six of seven studies, but not in one study of liver cells of cynomolgus monkeys in vivo. Di(2-ethylhexyl) phthalate treatment of Syrian hamster embryo cells in a two-stage exposure with 12-O-tetradecanoylphorbol 13-acetate resulted in superinduction of ornithine decarboxylase, an early event in morphological transformation no effect was seen after a one-stage treatment with di(2-ethylhexyl) phthalate alone. 

Unscheduled DNA synthesis was not induced in either mouse or hirman primary hepatocyte cultures with mono(2-ethylhexyl) phthalate, and neither this metabolite nor 2-ethylhexanol induced mutations in mouse lymphoma cells in vitro. Mono(2-ethyl-hexyl) phthalate induced sister-chromatid exchange in Chinese hamster V79 cells and chromosomal aberrations in Syrian hamster embryo cells. It also induced transformation in Syrian hamster embryo cells, but not in mouse C3H10T /2 cells. Gap-junctional intercellular communication was inhibited by mono(2-ethylhexyl) phthalate in Syrian hamster embryo cells and in Chinese hamster V79 cells. As reported in an abstract (Baker et al., 1996), this function was also inhibited in rat and mouse hepatocytes, but not in Syrian hamster or human hepatocytes. 

Baker, T.K., Kalimi, G.H., Lington, A.W., Isenberg, J.S., Klaunig, J.E. Nikiforov, A.I. (1996) Gap junctional intercellular communication (GJIC) studies on 5 phthalate monoesters in hepatocytes of four species implications for cancer risk assessment (Abstract). Toxicologist, 30, 208... 

Kang K-S, Wilson MR, Hayashi T, et al. 1996. Inhibition of gap junction intercellular communication in normal human breast epithelial cells after treatment with pesticides, PCBs, and PBBs, alone or in mixtures. Environ Health Perspect 104(2) 192-200. 

In cultured mammalian cells, acrylonitrile induced DNA strand breakage, gene mutation, sister chromatid exchanges and chromosomal aberrations, but not aneuploidy or unscheduled DNA synthesis in rat hepatocytes, at least if the silver grain counting method was used. [Studies using the less reliable scintillation counting method have not been summarized.] Cell transformation was induced in several test systems and gap-junctional intercellular communication was inhibited in one study with Chinese hamster V79 cells. 

Benzoyl peroxide generally inhibits gap-junctional intercellular communication in cultured cells. In contrast, an increase in gap-junctional intercellular communication was observed in a Syrian hamster embryo cell line. Changes in the expression of gap-junctional proteins (connexins) concomitant with inhibition of gap-junctional intercellular communication have been observed. In SEN mice treated with 83 jmol benzoyl peroxide, keratinocytes expressed the gap-jimctional connexin 26 gene (not normally expressed in adult mouse skin), transiently increased the expression of connexin 43 and reduced the expression of connexin 31.1 (Budunova et al., 1995, 1996). In primary mouse kerati-nocyte cultures, benzoyl peroxide strongly decreased the amount of E-cadherin protein (Jansen etal., 1996). 

Medical Economics Co. (1996) Physicians Desk Reference, 50th Ed., Montvale, NJ Mikalsen, S.O. Sanner, T. (1994) Increased gap junctional intercellular communication in... 

Toluene did not enhance morphological transformation of Syrian hamster embryo cells by the SA7 adenovirus or, as reported in an abstract, disruption of gap-junctional intercellular communication in Chinese hamster V79 cells (Awogi et al., 1986). 

Genotoxicity studies with A-hydroxyacetamide, a possible metabolite of acetamide, have shown that this agent is weakly mutagenic in Salmonella typhimurium and induces DNA damage in a rat hepatoma cell line. However, it did not bind covalently to DNA in vitro and did not induce morphological transformation of Syrian hamster embryo cells in vitro or inhibit gap-junctional intercellular communication in Chinese hamster lung V79 cells. 

Kim JH, Lee BK, Lee KW, Lee HJ. 2008. Resveratrol counteracts gallic acid-induced down-regulation of gap-junction intercellular communication. J Nutr Biochem. (Epub ahead of print)... 

Nielsen M, Ruch RJ, Yang O. 2000. Resveratrol reverses tumor-promoter-induced inhibition of gap-junctional intercellular communication. Biochem Biophys Res Commun 275 804-809. 

Upham BL, Guzvic M, Scott J, Carbone JM, Blaha L, Coe C, Li LL, Rummel AM, Trosko JE. 2007. Inhibition of gap junctional intercellular communication and activation of mitogen-activated protein kinase by tumor-promoting organic peroxides and protection by resveratrol. Nutr Cancer 57 38-47. 

Chinese hamster fibroblasts Gap junction intercellular communication + NS Malcolm and Mills 1989... 

PPAR a receptor, gap junctional intercellular communication, and replicative DNA synthesis (Isenberg et al. 2000, 2001 Smith et al. 2000). Two major mechanisms have been proposed to account for peroxisome proliferator-induced hepatocarcinogenicity in rodents induction of sustained oxidative stress and enhanced cell proliferation and promotion. Suppression of hepatocellular apoptosis has also been suggested to play a role. 

It has been hypothesized that nongenotoxic chemicals such as DEHP affect reproduction and development via the modulation (inhibition) of gap junctional intercellular communication, as proposed for liver tumor promotion (Rosenkranz et al. 2000 Trosko and Chang 1988 Trosko et al. 1998)... 

Isenberg JS, Kamendulis LM, Smith JH, et al. 2000. Effects of Di-2-Ethlhexyl phthalate (DEHP) on gap-junctional intercellular communication (GJIC), DNA synthesis, and peroxisomal beta oxidation (PBOX) inrat, mouse, and hamster liver. Toxicol Sci 56 73-85. 

McKee RH. 2000. The role of inhibition of gap junctional intercellular communication in rodent tumor induction by phthalates review on selected phthalates and the potential relevance to man. Regul Toxicol Pharmacol 32 51-55. 

Rosenkranz HS, Pollack N, Cunningham AR. 2000. Exploring the relationship between the inhibition of gap junctional intercellular communication and other biological phenomena. Carcinogenesis. 21(5) 1007-1011. 

SaiK, Kanno J, Hasewaga R, et aL 2000. Prevention of the down-regulation of gap junctional intercellular communication by green tea in the liver of mice fed pentachlorophenoL Carcinogenesis. 21 1671-1676. 

---