Tissue and sex-dependent differences in CYP2A activities in hamsters

Pelkonen, Paivi, Lang, Matti and Pasanen, Markku (1994) Tissue and sex-dependent differences in CYP2A activities in hamsters. Archives of Toxicology, 68 7: 416-422. doi:10.1007/s002040050091


Author Pelkonen, Paivi
Lang, Matti
Pasanen, Markku
Title Tissue and sex-dependent differences in CYP2A activities in hamsters
Journal name Archives of Toxicology   Check publisher's open access policy
ISSN 0340-5761
1432-0738
Publication date 1994-07
Sub-type Article (original research)
DOI 10.1007/s002040050091
Volume 68
Issue 7
Start page 416
End page 422
Total pages 7
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Abstract Three enzymatic activities of the CYP2A subfamily, coumarin 7-hydroxylase (COH), testosterone 15α-hydroxylase (T15αOH) and testosterone 7α-hydroxylase (T7αOH), were characterized in liver, kidney and lung microsomes from control, pyrazole (PYR), 3-methylcholanthrene (MC) and phenobarbital (PB) treated female and male Syrian golden hamsters. Sex-dependent changes in the enzymatic activities were found. Among control animals COH and T15αOH activities were higher in males. T7αOH activity was five times higher in female kidneys than in males. Inducers changed this metabolic profile. MC and PB were potent CYP2A inducers in extrahepatic tissues: significant increases were found in COH (5-fold) and T15αOH (12-fold) activities in female MC lung microsomes and T7αOH (7-fold) in MC male kidney microsomes. PB increased significantly activities of COH (5-fold), T15αOH (3-fold) and T7αOH (10-fold) in male kidney microsomes. All inducers significantly increased T7αOH activity in male kidney microsomes but decreased hepatic T7αOH activity in both sexes. PYR treatment decreased hepatic CYP2A activities. Anti-mouse CYP2A4/5 antibody inhibited COH activity by a variable extent depending on the tissue and pretreatment and recognised three 52-, 49-, 48-kDa bands in liver and two major bands in kidney (48 and 49 kDa) and lung (49 and 52 kDa) microsomes. COH and T15αOH activities correlated well with 49 kDa protein (r = 0.95 and r = 0.99, respectively) in lung microsomes. These results suggest that i) the inducibility and immunological characteristics of CYP2A activities in hamster tissues are clearly different compared with those found in mouse, ii) MC and PB are potent CYP2A inducers in extrahepatic tissues of hamsters, and iii) that extrahepatic CYP2A activities exhibit remarkable tissue- and sex-dependent differences in their response to chemical inducers.
Keyword Cytochrome P450
Extrahepatic monooxygenases
Induction
Metabolism
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: Mon, 30 Nov 2009, 15:07:17 EST