Tissue-specific expression of hormonal carcinogenesis target genes in rats treated with polycyclic aromatic hydrocarbons
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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.
KeywordsCYP1A1 CYP1B1 CYP19 ERα cyclinD1 hormonal carcinogenesis
- 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
- 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
- 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
- 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