Comparison of hamster and mouse reveals interspecies differences in the regulation of hepatic CYP2A isozymes

Pelkone, Päivi, Honkakoski, Paavo, Geneste, Olivier, Bartsch, Helmut and Lang, Matti A. (1993) Comparison of hamster and mouse reveals interspecies differences in the regulation of hepatic CYP2A isozymes. Biochemical Pharmacology, 46 10: 1681-1687. doi:10.1016/0006-2952(93)90571-D


Author Pelkone, Päivi
Honkakoski, Paavo
Geneste, Olivier
Bartsch, Helmut
Lang, Matti A.
Title Comparison of hamster and mouse reveals interspecies differences in the regulation of hepatic CYP2A isozymes
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
1873-2968
Publication date 1993-11-01
Sub-type Article (original research)
DOI 10.1016/0006-2952(93)90571-D
Open Access Status Not Open Access
Volume 46
Issue 10
Start page 1681
End page 1687
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Abstract Three CYP2A-related activities [coumarin 7-hydroxylase (COH), testosterone 7α- (test7α) and 15α-hydroxylases (test15α)], identified in hamster liver and analysed by immunoinhibition, and western and northern blotting, were found to be similar to mouse and human CYP2As. In the microsomal fractions, anti-mouse CYP2A5 antibody recognised three bands of about 48, 49 and 52 kDa, suggesting the presence of at least three proteins immunologically similar to mouse CYP2A5. The 49 kDa band migrated close to mouse CYP2A5 and changes in its expression followed COH and test15α activities. Test7α activity did not associate with any of the individual bands detected on western blots despite its strong inhibition by the antibody. Despite the immunological and catalytic similarities between mouse and hamster CYP2A enzymes, their regulation is different. In mice, the enzyme activities are higher in females than males, are induced by pyrazole (PY) and phenobarbital (Pb), and are not affected by 3-methylcholanthrene (MC). In hamsters, activities are not higher in females, induced by MC and reduced by PY. MC and PY appear to regulate expression at the mRNA level, while Pb seems to act post-transcriptionally by increasing either the synthesis or the stability of the protein. Our data indicate that the modes of expression and regulation of CYP2A-related enzymes make the hamster different from mice and humans with respect to the mechanism of metabolism of certain drugs and carcinogens.
Keyword Human liver fluke
Coumarin 7-hydroxylase
3 methylcholanthrene;
Coumarin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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Created: Tue, 01 Dec 2009, 01:07:03 EST