Induction of cytochromes P450 1A, 2B and 2E in hamster tissues by acetone
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The inductive effects of acetone on cytochromes P450 1A, 2B and 2E in liver, kidney and lung were studied using hamsters administered acetone in drinking water. Acetone administration caused five-, two- and sixfold increases of the activities of aniline hydroxylase, ethoxyresorufin O-dealkylase and pentoxyresorufin O-dealkylase in liver microsomes; eight- and twofold increases of aniline hydroxylation and ethoxyresorufin O-dealkylation in kidney; and a twofold increase of aniline hydroxylation in lung, respectively. Immunoblot analyses of microsomal proteins using mouse monoclonal antibody 1-12-3 to rat P450 1A1 and rabbit antibody to human P450 2E1 revealed that acetone resulted in about three-, four- and twofold increases of proteins immunorelated to P450s 1A and 2E in hamster liver, kidney, and lung, respectively. Protein blot analysis using mouse monoclonal antibody 2-66-3 to rat P450 2B1 showed that acetone caused five- and twofold increases, respectively, of an immunoreactive protein in hamster liver and kidney but decreased the P450 2B protein by 48% in lung. RNA blot analyses using cDNA probes derived from mouse P450 1A1 and rat P450 2B1 cDNA clones demonstrated that acetone elicited two- and twelvefold increases of the mRNA levels of P450s 1A and 2B in hamster liver, respectively. Northern blot analyses using oligonucleotide probes derived from hamster P450 2E1 cDNA sequence detected two species of hybridizable mRNA in control liver. Acetone preferentially caused a threefold increase in the level of the larger-sized mRNA. Acetone produced little increase or no effect on mRNAs of cytochromes P450 1A, 2B and 2E in kidney and lung. The present study demonstrates that acetone induces the catalytic activity, protein and mRNA levels of P450s 1A, 2B and 2E in hamster liver, and causes various changes of the P450 levels in kidney and lung. Acetone induction of hamster P450s 1A, 2B and 2E might involve transcriptional and post-transcriptional mechanisms.
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