Regular Article
Induction of CYP1A1 by Serum Independent of AhR Pathway

https://doi.org/10.1006/bbrc.1999.1959Get rights and content

Abstract

CYP1A1 is implicated in the bioactivation of procarcinogens such as polycyclic aromatic hydrocarbons. To date, no physiological compounds have been described as inducers of this gene. In this study, we have examined the role of serum in the regulation of CYP1A1 gene expression. After treatment of CaCo-2 cells with fetal bovine serum, CYP1A1 mRNA level increased to the same extent as that observed after 3-methylcholanthrene induction. The same effect was obtained after treatment with adult bovine or human serum. Evaluation of hnRNA level performed on CaCo-2 cells indicates that CYP1A1 induction by serum acts at least in part through transcriptional activation. Promoter region containing the XRE (1.56 kb) was tested in the CAT assay. No stimulation of this reporter gene was detected after serum treatment. These results demonstrate for the first time that physiological compound(s) contained in serum induces CYP1A1 gene expression by transcriptional activation independent of the AhR pathway.

References (35)

  • F.J. Gonzalez

    Pharmacol. Ther.

    (1990)
  • D.W. Nebert et al.

    Int. J. Biochem.

    (1989)
  • K. Kawajiri et al.

    Crit. Rev. Oncol. Hematol.

    (1993)
  • A.B. Okey et al.

    Trends Pharmacol. Sci.

    (1994)
  • G.H. Perdew

    J. Biol. Chem.

    (1988)
  • H.S. Chen et al.

    J. Biol. Chem.

    (1994)
  • M.S. Denison et al.

    J. Biol. Chem.

    (1988)
  • A. Raha et al.

    Arch. Biochem. Biophys.

    (1995)
  • I. Pongratz et al.

    J. Biol. Chem.

    (1992)
  • C. Vaziri et al.

    J. Biol. Chem.

    (1996)
  • S. Ferrari et al.

    Biochem. Biophys. Res. Commun.

    (1990)
  • M. Daujat et al.

    Biochem. Biophys. Res. Commun.

    (1992)
  • D.R. Nelson et al.

    Pharmacogenetics

    (1996)
  • D.W. Nebert et al.

    Annu. Rev. Biochem.

    (1987)
  • T.L. McLemore et al.

    J. Natl. Cancer Inst.

    (1990)
  • A. Hirvonen et al.

    Cancer Epidemiol. Biomarkers Prev.

    (1992)
  • F.P. Guengerich et al.

    Mutat. Res.

    (1998)
  • Cited by (31)

    • Collagen density regulates xenobiotic and hypoxic response of mammary epithelial cells

      2015, Environmental Toxicology and Pharmacology
      Citation Excerpt :

      Lastly, in Fig. 4E–H, we show that both DFOM and tranilast enhanced CYP1A1 and CYP4B1 expression in the MCF10A cell line. Thus, unlike VEGF production and the HRE response (Figs. 1–3), the regulation of P450 enzymes does not match the XRE response, suggesting that in non-tumorigenic cells, additional cell signals other than the AhR:ARNT pathway, may also play role in the regulation of P450 expression as has been previously explored (Guigal et al., 2000; Mastyugin et al., 2004; Zordoky and El-Kadi, 2009; Villard et al., 2011). To examine the mechanisms of P450 and VEGF expression in collagen, downstream signals associated with cell adhesion to collagen were assessed.

    • Fetal bovine serum and human constitutive androstane receptor: Evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system

      2014, Toxicology and Applied Pharmacology
      Citation Excerpt :

      In another study, hexanal, a peroxidation product of linoleic acid in FBS, was reported to activate peroxisome proliferator-activated receptor α (Villard et al., 2011), and this leads to an increase in peroxisome proliferator-activated receptor α-mediated induction cytochrome P450 1A1 (Villard et al., 2011). In contrast, FBS does not activate the aryl hydrocarbon receptor (Guigal et al., 2000; Guigal et al., 2001), which is a principal regulator of cytochrome P450 1A1 (Kohle and Bock, 2009). Overall, it appears that FBS selectively activates receptors by the action of various chemicals, including specific contaminants and metabolic breakdown products present in the serum.

    View all citing articles on Scopus
    1

    To whom correspondence should be addressed. E-mail: [email protected].

    View full text