Previously, it has been demonstrated that @entity1301 (NP) has a dual function in regulating reproductive hormones by: (1) increasing the activity of @entity134 metabolizing enzymes at low concentration, that does not induce @entity54193 ( @entity54193 ) and zona radiata proteins and (2) decreasing the activity of these enzymes at higher concentration [Environ. Health Perspect. 105 (1997) 109; Environ. Toxicol Chem. 16 (1997) 2576]. To more precisely understand the estrogenic effects of NP in fish and a possible interference with @entity134 hormone metabolism, we investigated in the @entity12178 the identity of the cytochrome P450 enzymes involved in NP hydroxylation. Up to 9 metabolites were separated by radio-HPLC when [R-(14)C]-4n-NP was incubated with hepatic microsomes from juvenile salmon. In control fish the major metabolites were identified as monohydroxylated products at omega-, (omega-1)- and (omega-2)-positions of the alkyl chain of 4n-NP. Salmon hepatic microsomes formed omega-, (omega-1)- and (omega-2)-lauric acid (LA) hydroxylation products. The potency of @entity10978 , @entity3102 and @entity2082 (non-specific, but strong inhibitors of CYP1A, 2K and 3A, respectively) on LA and NP hydroxylations were assessed in the present study. @entity3102 inhibited omega-, (omega-1)- and (omega-2)-hydroxylations of LA and 4n-NP and was the only inhibitor of omega-hydroxylation of both substrates. @entity2082 specifically inhibited (omega-1)- and (omega-2)-hydroxylations of LA as well as 4n-NP. Interestingly, the lowest NP dose (1 mg/kg) was the most potent inducer of NP-metabolites formation. These results suggest the involvement of CYP2M- and 2K-like enzymes in terminal and subterminal hydroxylations of 4n-NP respectively, and was confirmed by the competitive inhibition between LA and 4n-NP. The production of one unidentified 4n-NP metabolite was not affected by any of the chemicals used, suggesting a possible ring hydroxylation with involvement of another cytochrome P450 isoform. Our data reveal a novel aspect of CYP isozymes involvement in NP metabolism that may complicate the assessment of its endocrine effects. Hence, the regio-selective hydroxylation of endocrine disruptors, such as NP, by CYP isozymes is revealed as a possible new marker of estrogenicity.

Regio-specific hydroxylation of XXXX and the involvement of CYP2K- and CYP2M-like iso-enzymes in @entity12178 ( @entity12178 ).

@entity3102 :: ('MESH:D007654', 'Chemical') :: ['ketoconazole', 'Ketoconazole'] @entity2082 :: ('MESH:D004997', 'Chemical') :: ['Ethynylestradiol', 'ethynylestradiol'] @entity12178 :: ('8030', 'Species') :: ['Atlantic salmon'] @entity134 :: ('CHEBI:35341', 'Chemical') :: ['steroid'] @entity54193 :: ('100136426(Tax:8030)', 'Gene') :: ['Vtg', 'vitellogenin'] @entity10978 :: ('MESH:C011512', 'Chemical') :: ['alpha-naphthoflavone'] @entity1301 :: ('MESH:C025256', 'Chemical') :: ['nonylphenol']
@entity1301 :: (MESH:C025256,Chemical) :: ['nonylphenol']
