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Biomeditsinskaia khimiia

[mRNA level and cytochrome P450 1A activity in the liver of C57BL mice induced by various xenobiotics].


PMID 14562683

Abstract

The rate of hepatic cytochrome P450 Cypla1 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 Cypla1 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 Cypla2 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 Cypla were also investigated in liver. The increase of Cypla1 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 Cypla2 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 Cypla2 regulation. During induction with AQ the Cypla1 mRNA level remained unchanged, but the EROD activity increased almost 20-fold. The latter suggests insufficient specificity of this substrate for Cypla1. Thus, on the basis of the data obtained, the mRNA level can be considered as more accurate estimation of Cypla1 and Cypla2 inducibility, than the determination of the enzyme activity.

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