Altered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30 min or 24 h, and then exposed to GJIC-inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]. Out of nine CPAs tested, quercetin and silibinin elicited the most pronounced effects, preventing the dysregulation of GJIC by all the GJIC inhibitors, but DDT. Metformin and curcumin attenuated the effects of three GJIC inhibitors, whereas the other CPAs prevented the effects of two (diallyl sulfide, emodin) or one (indole-3-carbinol, thymoquinone) GJIC inhibitor. Significant attenuation of chemically induced inhibition of GJIC was observed in 27 (50%) out of 54 possible combinations of nine CPAs and six GJIC inhibitors. Our data demonstrate that in vitro evaluation of GJIC can be used as an effective screening tool for identification of chemicals with potential chemopreventive activity.
- MeSH
- antikarcinogenní látky farmakologie MeSH
- DDT toxicita MeSH
- epitelové buňky účinky léků MeSH
- fluoreny toxicita MeSH
- fluorokarbony toxicita MeSH
- hexachlorcyklohexan toxicita MeSH
- játra cytologie účinky léků MeSH
- kapryláty toxicita MeSH
- karcinogeny toxicita MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- kurkumin farmakologie MeSH
- metformin farmakologie MeSH
- mezerový spoj účinky léků metabolismus MeSH
- mezibuněčná komunikace účinky léků MeSH
- potkani inbrední F344 MeSH
- tetradekanoylforbolacetát toxicita MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of this work was to compare in vitro nitric oxide (NO) production by rat, bovine and porcine macrophages. NO production was induced by lipopolysaccharide (LPS) or by phorbol 12-myristate 13-acetate (PMA) with ionomycin or recombinant interferon gamma (rIFN-gamma) and was assessed by Griess reaction. NO synthase type II (NOS II) expression was quantified by immunocytochemistry, Western blot and real-time polymerase chain reaction (RT-PCR). There were differences in NO production by pulmonary alveolar macrophages (PAM) in all species tested. The largest amounts of NO were produced by rat PAM. Less NO was produced by bovine PAM. Moreover, PAM in rats and cows differed in their abilities to respond to various stimulators. Neither porcine PAM nor Kupffer cells produced NO. Stimulation of porcine PAM with alternative concentrations of LPS did not lead to inducing NO production. Stimulation of porcine PAM with rIFN-gamma together with LPS led to a significant increase in the expression of NOS II mRNA, albeit without detectable NO production or NOS II expression on the protein level.
- MeSH
- alveolární makrofágy metabolismus patologie MeSH
- biotest MeSH
- ethylendiaminy MeSH
- financování organizované MeSH
- imunohistochemie MeSH
- interferon gama toxicita MeSH
- ionomycin toxicita MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- lipopolysacharidy toxicita MeSH
- messenger RNA metabolismus MeSH
- oxid dusnatý analýza metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prasata MeSH
- regulace genové exprese enzymů MeSH
- skot MeSH
- sulfanilamidy MeSH
- synthasa oxidu dusnatého, typ II genetika metabolismus MeSH
- tetradekanoylforbolacetát toxicita MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- skot MeSH
- zvířata MeSH
