1. Institute of Molecular Biology and Biophysics, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk Institute of Bioorganic Chemistry, Siberian Branch of the Russian Academy of Sciences 2. Novosibirsk Institute of Bioorganic Chemistry, Siberian Branch of the Russian Academy of Sciences 3. Institut of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences 4. Institute of Molecular Biology and Biophysics, Siberian Branch of the Russian Academy of Medical Sciences
Abstract: The rate of hepatic cytochrome P450 Cyp1a1 and Cyp1a2 induction was investigated in C57BL male mice during induction with o-aminoazotoluene (OAT), benzo[a]pyrene (BP) and 1,4-dihydroxyanthraquinone (AQ). The Cyp1a1 mPNA level determined by quantitative RT-competitive PCR increased more than three orders of magnitude during induction with OAT and BP compared with untreated animals and remained unchanged during induction with AQ. The Cyp1a2 mRNA level was only 8.5, 18.7 and 1.9 times higher during induction with OAT, BP and AQ respectively than in untreated mice. At the same time 7-Ethoxyresorufin-O-deethylase (EROD) and 7-Methoxyresorufin-O-demethylase (MROD) activities of Cyp1a were also investigated in liver. The increase of Cyp1a1 mRNA level correlated with the increase of EROD activity. This suggests involvement of the transcriptional mechanism of the inducibility of this enzyme. In the case of Cyp1a2 there was insignificant increase of its mRNA level but high catalytic activity registered in liver in response to injection of the inductor of MR metabolism. This can imply the posttranscriptional mechanism of Cyp1a2 regulation. During induction with AQ the Cyp1a1 mRNA level remained unchanged, but the EROD activity increased almost 20-fold. The latter suggests insufficient specificity of this substrate for Cyp1a1. Thus, on the basis of the data obtained, the mRNA level can be considered as more accurate estimation of Cyp1a1 and Cyp1a2 inducibility, than the determination of the enzyme activity.
Reference: Mikhailova O.N., Filipenko M.L., Timofeeva O.A., Kaledin V.I., Gulyaeva L.F., Lyakhovich V.V., The mRNA level and the activity of the cytochrome P450 1a in liver of C57BL mice during induction with different xenobiotics, Biomeditsinskaya khimiya, 2003, vol:
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