Benzo[a]pyrene-dependent activation of transcription factors NF-kappaB and AP-1 related to tumor promotion in hepatoma cell cultures.
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.
Bolotina
N A
NA
Blokhin Institute of Carcinogenesis, Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow 115478, Russia.
Gasparian
A V
AV
Dubovaja
T K
TK
Evteev
V A
VA
Kobliakov
V A
VA
D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001580:Benzopyrenes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001580:Benzopyrenes; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011084:Polycyclic Aromatic Hydrocarbons; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D001564:Benzo(a)pyrene; C026487:benzo(e)pyrene