title: Expression of microRNAs, CYP1A1 and CYP2B1 in the livers and ovaries of female rats treated with DDT and PAHs.
abstract: OBJECTIVE
  In this study, we determined the expression level of miRNAs and the induction of CYP1A1 and CYP2B1 in the livers and ovaries of female Wistar rats treated with DDT, benzo[a]pyrene (BP), and 3-methylcholanthrene (MC). This study compared CYP1A/2B induction and miRNA expression levels to cast light on a possible role of miRNA in the tissue-specific induction of CYPs.
  
  
  METHODS
  The induction of CYP1A1/2B1 enzymes was detected by ethoxy-, pentoxyresorufin O-dealkylation and Western blot analysis. The CYP1A1/2B1 gene expression was determined by RT-real time PCR. Relative levels of expression for selected in silico miR species were determined by real time PCR with small nuclear U6 RNA employed as a reference gene.
  
  
  RESULTS
  After bioinformatic analysis, miR-21, 221, 222, and 429 were chosen as potential post-transcriptional regulators of rat CYP1A and CYP2B. It was shown that miR-21, 221, 222, and 429 expression levels decreased in the liver of DDT-, BP-, and MC-treated rats, whereas increases were observed in CYP1A1 and CYP2B1 mRNA expression levels and protein content, and EROD and PROD activities. Conversely, a tendency for elevated levels of miRNAs in the ovaries of inducer-treated female rats was observed. In the ovaries, a high level of CYP1A1 and CYP2B1 mRNA expression was observed, although protein content and enzyme activity were not visible.
  
  
  CONCLUSIONS
  These data suggest a potential involvement of miRNA in the post-transcriptional regulation of CYP1A and CYP2B in the livers and ovaries of chemically induced rats.
authors.affiliation: Institute of Molecular Biology and Biophysics, Siberian Branch of Russian Academy of Medical Sciences, Timakova 2, Novosibirsk 630117, Russia.
authors.forename: M D
authors.initials: MD
authors.lastname: Chanyshev
authors.affiliation: Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
authors.forename: N I
authors.initials: NI
authors.lastname: Kosorotikov
authors.affiliation: Institute of Molecular and Cell Biology, Siberian Branch of Russian Academy of Sciences, Lavrenteva 8/2, Novosibirsk 630090, Russia; ZAO VECTOR-BEST, Novosibirsk 630117, Russia.
authors.forename: S E
authors.initials: SE
authors.lastname: Titov
authors.affiliation: Institute of Molecular and Cell Biology, Siberian Branch of Russian Academy of Sciences, Lavrenteva 8/2, Novosibirsk 630090, Russia; Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
authors.forename: N N
authors.initials: NN
authors.lastname: Kolesnikov
authors.affiliation: Institute of Molecular Biology and Biophysics, Siberian Branch of Russian Academy of Medical Sciences, Timakova 2, Novosibirsk 630117, Russia; Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
authors.forename: L F
authors.initials: LF
authors.lastname: Gulyaeva
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis*; D003634:DDT / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D035683:MicroRNAs; D011084:Polycyclic Aromatic Hydrocarbons; D003634:DDT; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1
keywords: 3-Methylcholanthrene; 3-Methylcholanthrene (PubChem CID: 1674); Benzo[a]pyrene; Benzo[a]pyrene (PubChem CID: 611); CYP1A1; CYP2B1; DDT; DDT (PubChem CID: 3036); Expression level; PAH; Rat; miRNA