title: Increased gap junctional intercellular communication in Syrian hamster embryo cells treated with oxidative agents.
abstract: The effects of K2CrO4, H2O2, benzoyl peroxide, menadione, KBrO3 and UV365nm on gap junctional intercellular communication (GJIC) have been studied in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-sensitive Syrian hamster embryo (SHE) cell line BPNi. All agents were found to increase the level of GJIC by 50-100%. Also, in early passage SHE cells, a tendency for increased GJIC was found for the oxidative agents studied. Hydrogen peroxide was used as a model compound in the subsequent studies. The increase in GJIC was reversible, and it was not due to an increased non-junctional permeability. Hydrogen peroxide counteracted the TPA-induced decrease in GJIC, regardless of whether the cells were exposed to the compounds simultaneously or the cells were pre-exposed to TPA before addition of H2O2. The GJIC enhancement by H2O2 was slightly reduced by the addition of the hydroxyl radical scavenger dimethylsulphoxide or by the inhibition of catalase by amitrole. The cAMP/protein kinase A system is the only characterized signal transduction system that is known to increase GJIC in most cell types. Hydrogen peroxide did not increase the amount of cAMP (or cGMP) in BPNi cells, while forskolin and a phosphodiesterase inhibitor had to increase the cAMP level several-fold to affect GJIC to the same degree as the oxidative agents. Some inhibitors of protein kinase A were assayed for their ability to inhibit the increases in GJIC caused by H2O2 and forskolin. Staurosporine inhibited the forskolin-induced increase in GJIC, with much less effect on the H2O2-induced increase. H8, H88 and H89 had less effect than staurosporine on the forskolin-induced increase in GJIC. The results suggest that the cAMP/protein kinase A system may not be involved in the increase in GJIC caused by H2O2, although this cannot be completely ruled out.
authors.affiliation: Laboratory for Environmental and Occupational Cancer, Norwegian Radium Hospital, Oslo.
authors.forename: S O
authors.initials: SO
authors.lastname: Mikalsen
authors.forename: T
authors.initials: T
authors.lastname: Sanner
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004622:Embryo, Mammalian; D006861:Hydrogen Peroxide / Q000633:toxicity; D007365:Intercellular Junctions / Q000187:drug effects*; D008647:Mesocricetus; D016877:Oxidants / Q000633:toxicity*
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D006152:Cyclic GMP