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Appearance of Differentiation Characteristics (Induction of Ah-Receptor-Dependent Genes) during Cultivation of Transformed Cell Clone K8 from Embryonic Rat Fibroblasts

V. A. Evteev, A. V. Gasparian, N. P. Scherbak, and V. A. Kobliakov*

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

* To whom correspondence should be addressed.

Received October 28, 2008; Revision received December 4, 2008
The differentiation status of fibroblasts can be characterized by their ability to induce Ah-receptor-dependent genes. The ability to induce Ah-receptor-dependent genes encoding cytochrome P450 isoforms, Ah-receptor repressor, and NADPH-quinine oxidoreductase were studied in the transformed cell clone K8 obtained from immortalized embryonic rat fibroblasts by treatment with benzo(a)pyrene and in the parental clone F27. Treatment with benz(a)anthracene did not induce the genes in the transformed clone K8 on passages 4-14, but the induction was recorded in the transformed clone beginning from the 16th passage and later, whereas in F27 cells the induction was observed throughout the experiment. Induction levels of mRNA of the induction-regulating genes encoding the Ah-receptor and Ah receptor nuclear translocator were similar in F27 cells and in the transformed cell clone K8 in both early and late passages. Electrophoretic mobility shift assay showed that in clone K8 transmission of the induction signal was disturbed in the early passages before interaction of the activated Ah-receptor with the recognizing region of DNA. Possible mechanisms responsible for the absence of induction in the early passages in the transformed cells are discussed.
KEY WORDS: cell transformation, cytochrome P450, Ah-receptor, enzyme induction

DOI: 10.1134/S000629790911008X