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Expression of Rainbow Trout P450 Mrna in Response to Mixtures of B[a]p, Cadmium, and Estradiol
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| Abstract: | A great deal of uncertainty exists regarding the response of biological indicators of exposure to mixtures of chemical stressors. Enzymatic transformation systems that are exposed to xenobiotic insult may interact unpredictably when more than one stressor is present. In particular, monoxygenase and related enzymes may be down- or up-regulated, depending on the mix and concentration of chemicals present. The objectives of this study were to screen representatives of broad chemical classes for interactive effects on the monoxygenase P450 system, represented by the CYPIA1 gene. The chemicals benzo(a)pyrene, cadmium and estradiol were administered intraperitoneally, separately and in mixtures at various concentrations, following a block design, in sexually immature rainbow trout (O. mykiss). After 24 hours of exposure, liver tissue was removed and total RNA extracted for use in Reverse Transcription PCR. A set of PCR primers specific to rainbow trout were used to detect mRNA for CYPIA1. Analysis of relative mRNA expression revealed a 50% decrease in BaP-stimulated CYPIA1 by either estradiol or cadmium. When all three chemicals were combined, there was a further decrease of CYPIA1 mRNA expression to levels beyond those observed for estradiol plus BaP or cadmium plus BaP. The expression level observed, following the ternary exposure, represented approximately 10% of the expression stimulated by BaP alone. These combinations of chemical stressors represent plausible mixtures that may affect teleost physiological responses in ways not predicted by single chemical exposure systems. Moreover, regional evaluations of biological indicators may be skewed by false negatives when evaluating field populations for exposure to chemical stressors. The development of biological indicators of exposure will benefit from using chemical mixtures in exposure systems by identifying unrecognized mechanisms and interactions. |
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| Citation: | Lattier, D. L., J. S. Mcclain, and J. T. Oris. Expression of Rainbow Trout P450 Mrna in Response to Mixtures of B[a]p, Cadmium, and Estradiol. Presented at Society of Environmental Toxicology and Chemistry, Philadelphia, PA, November 12-14, 1999. |
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| Contact: |
Linda Ransick - (513) 569-7395 or ransick.linda@epa.gov
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| Division: |
Ecological Exposure Research Division |
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| Branch: |
Molecular Ecology Research Branch |
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| Product Type: |
Abstrct/Oral |
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| Presented: |
11/13/1999 |
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