Elevated levels of cytochrome P4501A (CYP1A) in ringed seals from the Baltic Sea

Citation
M. Mattson et al., Elevated levels of cytochrome P4501A (CYP1A) in ringed seals from the Baltic Sea, AQUAT TOX, 43(1), 1998, pp. 41-50
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Aquatic Sciences
Journal title
AQUATIC TOXICOLOGY
ISSN journal
0166-445X → ACNP
Volume
43
Issue
1
Year of publication
1998
Pages
41 - 50
Database
ISI
SICI code
0166-445X(199809)43:1<41:ELOCP(>2.0.ZU;2-7
Abstract
The high frequency of a variety of disorders observed in Baltic seals have been correlated with elevated concentrations of organochlorines. For this s tudy, we determined hepatic CYP1A activities and apoprotein levels in ringe d seals (Phoca hispida) exposed to high levels of organochlorides in the Ba ltic Sea and in corresponding seals from a relatively unpolluted area (Sval bard Region). Activities of ethoxyresorufin deethylase (EROD) and pentoxyre sorufin depentylase (PROD) in seal liver microsomes were increased about 3- fold in the Baltic sample, the EROD activity reaching similar levels to tho se found in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced rats (about 1,2 nmo l/mg protein per min). No sex-related differences in EROD or PROD activitie s were observed in either population. Hepatic CYP1A levels in ringed seals were further characterised by inhibition and Western blot analysis. a-Napht hoflavone and furafylline were used as chemical inhibitors, having highly s pecific inhibiting effects on CYP1A1 and CYP1A2, respectively, in rat and h uman liver. cc-Naphthoflavone inhibited potently both EROD and PROD activit ies, while inhibition by furafylline was weaker. A monoclonal antibody spec ific to CYP1A in the rat (MAb 1-7-1), used in the immunoblots, revealed a s ubstantially increased amount of CYP1A protein in the Baltic seals. CYP2B-r elated proteins were not detected in any seal sample using MAb 2-66-3, whic h is specific for rat CYP2B. Thus, both inhibition and Western blotting exp eriments indicate that CYP1A is mainly responsible for the marked increase in microsomal EROD and PROD activities in the livers of Baltic ringed seals . Since the properties of all CYP enzymes vary between species, further stu dies are needed to verify whether CYP1A1 or CYP1A2 mediates the observed ER OD induction in the ringed seal. (C) 1998 Elsevier Science B.V. All rights reserved.