Cytochrome P4501A (CYP1A), a xenobiotic metabolizing enzyme found in allvertebrates, is highly induced following exposure to a number of organic contaminants.Several populations of teleosts residing in highly contaminated areas have been found toexhibit resistance to the toxic effects of contaminants, a condition characterized byreduced expression of CYP1A.Within this work I demonstrated that expression of CYP1A mRNA, protein, andactivity in caged rainbow trout (Oncorhynchus mykiss) was an effective biomarker ofpolychlorinated biphenyl (PCB) contamination. Furthermore, through the use of bothlaboratory and field studies, I demonstrated that several species inhabiting a PCBcontaminated site exhibited either acquired (Ameiurus natalis) or natural (Lepomiscyanellus) resistance to the CYP1A inducing effects of PCBs. Further studiescharacterized the response of several other Lepomis species to CYP1A inducingcompounds, demonstrating that the natural resistance of L. cynaellus is a characteristicshared by at least two other members of the genus. Lepomis species were relativelyinsensitive to CYP1A induction following PCB exposure yet exhibited highly inducedCYP1A levels following exposure to another CYP1A inducer, the model polyaromatichydrocarbon benzo[a]pyrene (BaP), suggesting a number of species within the genusLepomis may display natural resistance to certain classes of CYP1A inducingcompounds.Additional studies using responsive and resistant populations of killifish wereused to examine the consequences of resistance on fish physiology. Thyroid hormones,known to be altered by PCBs in mammals, were variable but did not differ significantlybetween responsive and resistant fish following PCB exposure. Treatment with PCBssuppressed production of the egg yolk precursor protein vitellogenin in primaryhepatocytes of responsive fish. Studies examining the developmental impacts of toxicantexposure demonstrated altered aspects of development in PCB responsive but notresistant Fundulus heteroclitus embryos exposed to polybrominated diphenyl ethers(PBDEs), compounds structurally related to PCBs. PBDE exposure in juvenile Ictaluruspunctatus failed to induce CYP1A or uridine diphosphate glucuronyltransferase(UDPGT) activity indicating PBDEs do not impact these commonly measuredtoxicological endpoints. The findings of this work describe novel pollutant responses in anumber of species with varying degrees of pollutant sensitivity and contribute to theunderstanding of toxicant induced alterations in teleost physiology.
| Identifer | oai:union.ndltd.org:uky.edu/oai:uknowledge.uky.edu:gradschool_diss-1275 |
| Date | 01 January 2005 |
| Creators | Brammell, Benjamin Frederick |
| Publisher | UKnowledge |
| Source Sets | University of Kentucky |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | University of Kentucky Doctoral Dissertations |
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