Altered enzyme expression in a population of creosote-resistant mummichog (Fundulus heteroclitus)
- Coll. of William and Mary, Gloucester Point, VA (United States). School of Marine Science
A population of mummichog in the Elizabeth River, Virginia inhabit a site severely contaminated with creosote. Although adult fish develop cancer, all life stages are resistant to the acute effects of creosote-contaminated sediments. Creosote is a complex mixture of PAHs, N,S,O-heterocyclics and phenols. The site is also contaminated with other organic contaminants and metals. Studies are underway to identify possible resistance mechanisms in this population. Cytochrome P4501A (CYP1A) is the major enzyme involved in activation of PAHs and also contributes to generation of reactive oxygen species (ROS). This enzyme is depressed in liver of resistant fish and unresponsive to CYP1A inducers. Glutathione S-transferases (GSTs) are major cytosolic proteins involved in diverse detoxification mechanisms. GST levels and activity are clearly elevated in the resistant population. Monoclonal antibody to purified mummichog GST recognizes a form that is elevated approximately six-fold in the resistant fish relative to reference fish. This form appears to be a major cytosolic protein in the resistance population. P-glycoprotein, an efflux pump for diverse xenobiotics, is abundantly expressed on the canalicular surface of hepatocytes and over expressed in advanced hepatic lesions. The pattern of enzyme expression observed in the resistant population is similar to that observed in multidrug-resistant cell lines.
- OSTI ID:
- 460481
- Report Number(s):
- CONF-961149--
- Country of Publication:
- United States
- Language:
- English
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