Tissue-specific expression of hormonal carcinogenesis target genes in rats treated with polycyclic aromatic hydrocarbons

  • M. D. Chanyshev
  • V. O. Pustylnyak
  • L. F. Gulyaeva


We have investigated the effect of polycyclic aromatic hydrocarbons (PAHs) on expression of the estrogen-metabolizing genes CYP1A1, CYP1B1, CYP19 and also ERα, and cyclinD1 genes, regulating cell division in estrogen-depended tissues. Treatment of rats with benzo(a)pyrene (BP) or 3-methylcholantrene (MCA) significantly up-regulated CYP1A1, CYP1B1 gene expression in liver, uterus and ovary, whereas α-naphthoflavone (α-NF) did not have any effect. The high level of aromatase gene (CYP19) expression was detected in ovary only. Treatment of rats with BP or MCA significantly down-regulated expression of this gene (15- and 5,5-fold, respectively), whereas α-NF was ineffective. Administration of BP but not MCA or α-NF increased ERα and cyclinD1 gene expression in rat liver. The levels of ERα and cyclinD1 mRNA levels remained unchanged in uterus of after treatment of rats with these PAHs. BP administration increased ERα and cyclinD1 mRNA levels (3,5- and 2,5-fold, respectively) in ovary, while MCA and α-NF were ineffective. Thus, our results give evidence for tissue-specific effects of PAHs on expression of genes, which participate in hormonal carcinogenesis. On the other hand, the fact that BP and MCA treatments influenced the expression of estrogen-metabolizing genes and genes, which control cell division, supports the viewpoint that PAHs may be one of the causes of endocrine disorders and subsequent hormonal carcinogenesis.


CYP1A1 CYP1B1 CYP19 ERα cyclinD1 hormonal carcinogenesis 


  1. 1.
    Wogan, G.N., Hecht, S.S., Felton, J.S., Conney, A.H., and Loeb, L.A., Semin. Cancer Biol., 2004, vol. 14, pp. 473–486.CrossRefGoogle Scholar
  2. 2.
    Pisareva, L.F., Odintsova, I.N., Boyarkina, A.P., Cherdyntseva, N.V., Voevoda, M.I., Belyavskaya, V.A., Raputa, V.F., and Choinzonov, E.L., Sibirskyi Onkologicheskyi Zhurnal, 2009, vol. 6, pp. 28–36.Google Scholar
  3. 3.
    Kummer, V., Masková, J., Zral, Z., Neca, J., Simecková, P., Vondrácek, J., and Machala, M., Toxicol. Lett., 2008, vol. 180, pp. 212–221.CrossRefGoogle Scholar
  4. 4.
    Piersen, C.E., Integr. Cancer Ther., 2003, vol. 2, pp. 120–138.CrossRefGoogle Scholar
  5. 5.
    Miller, W.R. and Sharpe, R.M., Endocrine-Related Cancer, 1998, vol. 5, pp. 69–96.CrossRefGoogle Scholar
  6. 6.
    Plísková, M., Vondrácek, J., Vojtesek, B., Kozubík, A., Machala, M., Toxicol. Sci., 2005, vol. 83, pp. 246–256.CrossRefGoogle Scholar
  7. 7.
    Simpson, E.R. and Davis, S.R., Endocrinology, 2001, vol. 142, pp. 4589–4594.CrossRefGoogle Scholar
  8. 8.
    Bulun, S.E., Lin, Z., Imir, G., Amin, S., Demura, M., Yilmaz, B., Martin, R., Utsunomiya, H., Thung, S., Gurates, B., Tamura, M., Langoi, D., and Deb, S., Pharmacol. Rev., 2005, vol. 57, pp. 359–383.CrossRefGoogle Scholar
  9. 9.
    Shabani, N., Mylonas, I., Jeschke, U., Thaqi, A., Kuhn, C., Puchner, T., Friese, K., Anticancer Res., 2007, vol. 27, pp. 2027–2033.Google Scholar
  10. 10.
    Denison, M.S. and Nagy, S.R., Annu. Rev. Pharmacol. Toxicol., 2003, vol. 4, pp. 309–334.CrossRefGoogle Scholar
  11. 11.
    Cavalieri, E., Frenkel, K., Liehr, J.G., Rogan, E., and Roy, D., J. Natl. Cancer Inst. Monogr., 2000, vol. 27, pp. 75–93.Google Scholar
  12. 12.
    Ohtake, F., Takeyama, K., Matsumoto, T., Kitagawa, H., Yamamoto, Y., Nohara, K., Tohyama, C., Krust, A., Mimura, J., Chambon, P., Yanagisawa, J., Fujii-Kuriyama, Y., and Kato, S., Nature, 2003, vol. 423, pp. 545–550.CrossRefGoogle Scholar
  13. 13.
    Hellmold, H., Overvik, E., Strömstedt, M., and Gustafsson, J.A., Carcinogenesis, 1993, vol. 4, pp. 1751–1757.CrossRefGoogle Scholar
  14. 14.
    Stocco, C., Steroids, 2008, vol. 73, pp. 473–487.CrossRefGoogle Scholar
  15. 15.
    Lee, A.J., Cai, M.X., Thomas, P.E., Conney, A.H., and Zhu, B.T., Endocrinology, 2003, vol. 144, pp. 3382–3398.CrossRefGoogle Scholar
  16. 16.
    Baba, T., Mimura, J., Nakamura, N., Harada, N., Yamamoto, M., Morohashi, K., and Fujii-Kuriyama, Y., Mol. Cell. Biol., 2005, vol. 25, pp. 10040–10051.CrossRefGoogle Scholar
  17. 17.
    Dong, W., Wang, Lu., Thornton, C., Scheffler, B.E., and Willett, K.L., Aquatic Toxicology, 2008, vol. 88, pp. 289–300.CrossRefGoogle Scholar
  18. 18.
    Hutz, R.J., Carvan, M.J., Baldridge, M.G., Conley, L.K., and Heiden, T.K., Tren. Reprod. Bio., 2006, vol. 2, pp. 1–11.Google Scholar
  19. 19.
    Liu, S., Abdelrahim, M., Khan, S., Ariazi, E., Jordan, V.C., and Safe, S., Biol. Chem., 2006, vol. 387, pp. 1209–1213.CrossRefGoogle Scholar
  20. 20.
    Abdelrahim, M., Ariazi, E., Kim, K., Khan, S., Barhoumi, R., Burghardt, R., Liu, S., Hill, D., Finnell, R., Wlodarczyk, B., Jordan, V.C., and Safe, S., Cancer Res., 2006, vol. 66, pp. 2459–2467.CrossRefGoogle Scholar
  21. 21.
    Swedenborg, E., Rüegg, J., Hillenweck, A., Rehnmark, S., Faulds, M.H., Zalko, D., Pongratz, I., and Pettersson, K., Mol. Pharmacol., 2008, vol. 73, pp. 575–586.CrossRefGoogle Scholar
  22. 22.
    Routledge, E.J. and Sumpter, J.P., J. Biol. Chem., 1997, vol. 272, pp. 3280–3288.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • M. D. Chanyshev
    • 1
    • 2
  • V. O. Pustylnyak
    • 1
    • 2
  • L. F. Gulyaeva
    • 1
    • 2
  1. 1.Institute of Molecular Biology and BiophysicsSiberian Branch of Russian Academy of Medical SciencesNovosibirskRussia
  2. 2.Novosibirsk State UniversityNovosibirskRussia

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