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Correlation between Hepatocarcinogenic Effect of Estragole and Its Influence on Glucocorticoid Induction of Liver-Specific Enzymes and Activities of FOXA and HNF4 Transcription Factors in Mouse and Rat Liver

V. I. Kaledin1, M. Yu. Pakharukova1*, E. N. Pivovarova1, K. Yu. Kropachev1, N. V. Baginskaya1, E. D. Vasilieva1, S. I. Ilnitskaya1, E. V. Nikitenko2, V. F. Kobzev1, and T. I. Merkulova1

1Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, ul. Akademika Lavrentieva 10, 630090 Novosibirsk, Russia; fax: (383) 333-1278; E-mail: pmaria@yandex.ru

2333 Military Hospital of Ministry of Defense of the Russian Federation, ul. Voinskaya 1, 630017 Novosibirsk, Russia

* To whom correspondence should be addressed.

Received June 20, 2008; Revision received September 2, 2008
It is known that the carcinogenic effect of estragole, a component of essential oils of many spicy plants, is characterized by species, tissue, and sex specificity. It causes mainly liver tumors in female mice but is not carcinogenic for male mice and for rats. In this work, the estragole hepatocarcinogenicity was shown for female mice of previously not studied ICR line. The strict correlation between estragole hepatocarcinogenicity and its ability to decrease the level of glucocorticoid induction of liver-specific enzymes tyrosine aminotransferase (TAT) and tryptophan oxygenase (TO) was found. Inhibition of TAT and TO inducibility by estragole takes place only in female mice but not in male mice and in rats. Studying the estragole effect on DNA-binding activity of transcription factors, present mainly in liver and regulating expression of genes encoding liver-specific proteins, has shown that estragole decreases FOXA and HNF4 activities but not activities of C/EBP and HNF1, and this happens only in female mice, for which this substance is hepatocarcinogen, but not in male mice and in rats. Pentachlorophenol, preventing hepatocarcinogenic effect of estragole, abolishes inhibitory influence of the latter on the TAT and TO glucocorticoid induction and restores DNA-binding activity of FOXA and HNF4. Thus, a correlation was revealed between the estragole hepatocarcinogenic effect and decrease in DNA-binding activity of transcription factors FOXA and HNF4, which might be indicative of the role of these factors in tumor suppression mechanisms in liver.
KEY WORDS: hepatocarcinogens, estragole, tryptophan oxygenase, tyrosine aminotransferase, glucocorticoid induction, HNF4, FOXA

DOI: 10.1134/S000629790904004X