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710                                                        The Toxicology of Fishes


                                                Chemical exposure

                                              Chemical bioavailability

                                             Chemical–ligand binding

                                               Cellular metabolism


                                              Biochemical dysfunction

                                             Physiological dysfunction


                                  Apoptosis        Necrosis       Biochemical adaptation




                                                      Physiologic adaptation      DNA adduct
                                                                                   (mutation)

                                                        Cell and tissue
                                                     morphologic adaptation



                                   Whole-animal death      Whole-animal adaptation  Neoplasia
                       FIGURE 16.6 Cascade of histopathological alterations as result of biochemical and physiological alterations in an organ-
                       ism. (Adapted from Hinton, D.E. and Laurén, D.J., in Biological Indicators of Stress in Fish, Vol. VIII, Adams, S.M., Ed.,
                       American Fisheries Society, Bethesda, MD, 1990, pp. 51–66; Hinton, D.E. et al., in Biomarkers: Biochemical, Physiological,
                       and Histological Markers of Anthropogenic Stress, Huggett, R.J. et al., Eds., Lewis Publishers, Boca Raton, FL, 1992, pp.
                       155–209.)


                       contamination of aquatic ecosystems was first suggested by Dawe et al. (1964), who postulated that
                       liver neoplasms observed in white sucker and brown bullhead from Deep Creek Lake in Maryland might
                       have resulted from chemical exposure. Since that time, numerous wild fish tumor epizootics have been
                       identified in North America alone, dominated by liver tumors in bottom feeders in the vicinity where
                       chemical contaminants were concentrated. Pierce et al. (1978), for example, reported the occurrence of
                       hepatic tumors in English sole in Puget Sound in Washington. Malins et al. (1984) also studied sediment-
                       associated chemicals from near-coastal areas and related PAHs to the induction of tumors in marine fish
                       species. A good correlation, in fact, was found between the indices of hepatocellular  carcinoma or
                       papilloma of the fish examined and PAH sediment concentration. Likewise, Black (1983) reported that
                       a high prevalence of epidermal  papilloma, epidermal  carcinoma, and hepatocellular carcinoma was
                       observed in brown bullhead inhabiting the Buffalo River, in which sediment was contaminated with
                       PAHs. Harshbarger et al. (1993), and Moore and Myers (1994) provided additional fish histology
                       references focused on the pathobiology of chemical-associated neoplasia in aquatic organisms.
                        Morphological change can manifest itself in various external and internal lesions or diseases that can
                       be easily quantified (Au, 2004). External metrics include fin erosion, skeletal abnormalities, epidermal
                       hyperplasias, and opercular abnormalities (Au, 2004). In addition, a number of characteristics of ana-
                       tomical and cytological alterations favor the use of histological examination in the biomarker approach
                       (Myers and Fournie, 2002). With a thorough prior knowledge of normal anatomy, the use of histological
                       analysis can be used to detect chemically induced alterations in a variety of tissues and organs in many
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