AIMS: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. MAIN 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. KEY FINDINGS: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. SIGNIFICANCE: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.
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