Benzo[a]pyrene-Dependent Activation of Transcription Factors NF-kappaB and AP-1 Related to Tumor Promotion in Hepatoma Cell Cultures

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N. A. Bolotina^1,2#, A. V. Gasparian^1#, T. K. Dubovaja², V. A. Evteev¹, and V. A. Kobliakov^1*

¹Blokhin Institute of Carcinogenesis, Russian Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, 115478 Moscow, Russia; E-mail: kobliakov@rambler.ru

²Russian State Medical University, ul. Ostrovityanova 1, 117437 Moscow, Russia

^* To whom correspondence should be addressed.

^# These authors equally contributed in this work.

Received October 16, 2006; Revision received January 25, 2007

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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-êB 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.

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KEY WORDS: tumor promotion, cytochrome P450, Ah-receptor, NF-kappaB, AP-1

DOI: 10.1134/S0006297907050124

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