PT06 Contaminants-Receptor Interactions: New Challenges
Exhibit Hall
8:00 AM - Tuesday, 11 November 2003
(PT083) Lauric acid hydroxylation in catfish exposed to peroxisome proliferators clofibrate or 2,4-D.
Haasch, M1, Ford, A1, Allgood, J1, 1 The University of Mississippi, University, MS, USA
ABSTRACT- Peroxisome proliferators (PPs) include a broad range of structurally diverse chemicals, many of which are ubiquitous environmental contaminants (e.g. agrochemicals, solvents, plasticizers, pharmaceuticals, etc.). During peroxisome proliferation, shifts in metabolism are produced through induction of many enzymes involved in fatty acid metabolism, retinoid and steroid metabolism, and cellular energy production. Previously we have shown that adult catfish exposed by i.p. injection, to the PPs, clofibrate (CLO) or the more potent ciprofibrate (CPR), did not exhibit any changes in hepatic microsomal lauric acid hydroxylase (LA-OHase) activities, although kidney microsomal 
and -6 products were significantly increased. Induction of CYP2K1/2M1-like immunoreactive proteins in catfish by 48 hr i.p. injection of CLO and CPR has been shown (Haasch, 1996). Waterborne, 48 hr exposure of juvenile channel catfish (Ictalurus punctatus; size range 7.24 g to 34.32 g) to 1 ppm CLO (4.12 nM) or 2,4-dichlorophenoxyacetic acid (2,4-D; 4.52 nM) produced significant increases in both -1 and -5 hydroxylation products. Interestingly, -1 activity was absent in control and vehicle (DMSO) treated fish although we have previously shown that adults have relatively high -1 activity. Age and sex-dependent expression of LA-OHase activities in rainbow trout has previously been demonstrated (Buhler et al., 1997). We have also shown sex-specific hepatic microsomal LA-OHase activities in non-treated mature channel catfish. Taken together, these data indicate that juvenile channel catfish are sensitive to PPs, exhibiting changes in fatty acid metabolism. There is potential for sub-terminal hydroxylation products to act in cellular signal transduction. Exposure of developing fish to the many environmentally ubiquitous PPs may produce adverse effects. (Work supported by ES07929)
Key words: cytochrome P450, lauric acid hydroxylation, clofibrate, 2,4-dichlorophenoxyacetic acid