EFFECT OF ARYL HYDROCARBON RECEPTOR AGONISTS AND LIPOPOLYSACCHARIDE ON BENZO(A)PYRENE GENOTOXICITY MARKERS

The effect of aryl hydrocarbon receptor agonists (FICZ and ITE), as well as lipopolysaccharide under the toxic action of benzo(a)pyrene in HepaRG human hepatoma cells was evaluated. Active forms of the key stress-activated kinase cascades and DNA repair system proteins were used as markers of the genotoxic action of benzo(a)pyrene. A mixture of lipopolysaccharide with benzo(a)pyrene increases benzo(a)pyrene cytotoxicity and reduces the activation of DNA repair system proteins below the control level. Aryl hydrocarbon receptor agonists (FICZ and ITE) exhibit a cytoprotective effect against benzo(a) pyrene, enhance Akt1 kinase activation, and downregulate activation of the p53 protein and Chk1 and Chk2 checkpoint kinases. Thus, FICZ and ITE reduce the genotoxicity of benzo(a)pyrene.

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