Page 647 - The Toxicology of Fishes
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Toxicity Resistance                                                         627


                           of research needs to be revisited in light of recent advances in technology and advances in our
                           understanding of specific resistance mechanisms in insects and mammals (e.g., altered biotrans-
                           formation, altered toxicity targets).
                        •  Metals. Investigations of metal tolerance in fish populations have provided insight into processes
                           (i.e., acclimation vs. adaptation) and mechanisms of tolerance to metals. Most of these studies
                           indicate a strong relationship between tolerance to metals and upregulation of metal-binding
                           proteins, especially metallothioneins.
                        •  Dioxin-like compounds. A great deal of recent effort has focused on populations of mummichog
                           inhabiting sites (e.g., New Bedford Harbor) contaminated with dioxin-like compounds (DLCs).
                           A large body of evidence indicates that one or more components of the  aryl hydrocarbon
                           receptor (AhR) pathway are altered in these fish. Although the specific alterations in this
                           pathway have not been identified, continued active research in this area of research will likely
                           lead to success.
                        •  Creosote/PAHs. An altered AhR may also play a role in resistance of Atlantic Wood mummichog
                           to compounds associated with creosote. In addition, a pattern of protein and enzyme expression
                           resembling multidrug resistance in cancer suggests that a similar multi-xenobiotic-resistant
                           phenotype may contribute to survival in this population. These fish provide a model for studies
                           of multidrug (multi-xenobiotic) resistance that may have relevance to other exposed vertebrate
                           species.

                        Adaptation to chemical stress may come at a cost. Several recent reports suggest that adapted fish
                       maintained in clean laboratory environments have a reduced ability to respond to environmental
                       stressors (e.g., low oxygen, microbial exposure) or to perform (e.g., capture prey) when compared
                       with responses in observed normal individuals. Further studies are needed to establish specific rela-
                       tionships (e.g., pleiotropic relationships) between resistance and performance in actual field situations.
                       Expected associations between reduced genetic diversity and genetic adaptation may require recon-
                       sideration in light of observations made in adapted mummichog populations that maintained a high
                       level of genetic diversity.
                        Current research on toxicity resistance in fish has focused on a number of opportunistic fish species
                       that reside for most or all of their lives in highly contaminated sites. Future studies should include
                       investigations of the abilities and limitations of more sensitive species that may be capable of adapting
                       to moderately contaminated environments. These studies should focus on sensitive toxicity endpoints
                       such as reproduction, development, and behavior. Additional studies are needed on emerging contami-
                       nants (e.g., personal-care products, pharmaceuticals, wastewater organic contaminants) that likely exert
                       subtle effects during long-term, low-level exposures.
                        Tolerance has important consequences relative to population persistence and ecosystem function.
                       The mummichog has been the subject of extensive investigations on adaptation to environmental
                       variables (e.g., temperature) along large geographic and geological time scales (Place and Powers,
                       1979; Powers and Place, 1978; Powers et al., 1986). Studies on the effects on mummichog of chronic
                       exposure to persistent chemical contaminants will ultimately lead to a better understanding of the
                       impacts of these stressors on evolutionary processes. Genomic tools under development for this species
                       will advance progress in this area (Burnett et al., 2007). Additional research is also needed on physical
                       and biological environmental factors and on species attributes, such as genetic variation and life-stage-
                       specific dispersal characteristics, that may contribute to the development, maintenance, and costs of
                       adaptation to toxic pollutants.



                       Acknowledgment

                       This is contribution number 2869 from the Virginia Institute of Marine Science and contribution number
                       AED-04-015 from the U.S. Environmental Protection Agency ORD NHEERL Atlantic Ecology Division.
                       This manuscript has not been subjected to EPA review and does not necessarily reflect the views of the EPA.
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