The activation by the carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) of transcription factors NF-kappaB and AP-1 in hepatoma 27 and HepG2 cell cultures was studied. In contrast to the hepatoma HepG2 cells, cytochrome P450 isoforms and Ah-receptor are not expressed in the hepatoma 27 cells. The transcription factor NF-kappaB was activated only in the hepatoma 27 cells by BP treatment but not by its noncarcinogenic isomer benzo[e]pyrene (BeP). Conversely to NF-kappaB activation the transcription factor AP-1 was activated in the hepatoma HepG2 cells by cell treatment with BP but not in the hepatoma 27 cells. It is concluded that the NF-kappaB activation is caused by nonmetabolized BP molecule and not related to activation of the Ah-receptor. The transcription factor AP-1 seems to be activated as a result of the interaction of BP with the Ah-receptor. The realization of tumor promotion stage by carcinogenic PAHs treatment in dependence on the cytochrome P450 and Ah-receptor levels in the initiated cells is discussed.

The proliferative effect of some compounds that are aryl hydrocarbon (Ah) receptor ligands was studied on hepatoma 27 cells with absent expression of Ah receptor. Compounds of the polycyclic aromatic hydrocarbon (PAH) class benzo/a/pyrene, 3-methylcholanthrene, 7,12-dimethylbenz/a/anthracene, and benzo/e/pyrene as well as β-naphthoflavone (β-NF) and chlorinated hydrocarbon Aroclor 1254 were studied. It was found that carcinogenic PAH and β-NF stimulate cell proliferation both under conditions of standard serum content and in a medium with low serum content. More efficient stimulation of proliferation was observed in the case of low serum content. Aroclor 1254 and benzo/e/pyrene did not stimulate cell proliferation. Stimulation of proliferation was accompanied by activation of the ERK1/2-dependent MAP-kinase cascade. Benzo/a/pyrene caused a decrease in the number of cells in G1 phase of the cell cycle and increase in number of cells in G2/M phases under conditions of cell growth in media with low serum content. Carcinogenic PAH and β-NF activated transcription factor AP-1, and in this case activation was more pronounced in cells grown in medium with low serum content. A possible mechanism of activation of proliferation by an Ah receptor-independent pathway is discussed.

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