Page 328 - The Toxicology of Fishes

308 The Toxicology of Fishes

antioxidant genes such as superoxide dismutase, catalase, or glutathione peroxidase should not be
expected either in mammals or in fish. Future studies will be likely to examine the expression of genes
shown in mammals to respond strongly to oxidative stress but which have received less attention in fish
(e.g., heme oxygenase). Similarly, they may examine additional parameters and subcellular compart-
ments; for example, mitochondria are an important target of oxidative stress (Cadenas and Davies, 2000;
Finkel and Holbrook, 2000; Kowaltowski and Vercesi, 1999; Krumschnabel et al., 2005; Outten et al.,
2005; Yakes and Van Houten, 1997), but mitochondria or mitochondrial-specific parameters such as
MnSOD, mitochondrial glutathione pools, and mitochondrial GPX have received little attention. Molec-
ular characterization of antioxidant enzymes in fish may provide guidance by demonstrating which genes
are ARE regulated and which are not. Future studies should also take into account (through experimental
design and/or statistical analysis) as much as possible the effects of confounding biological and envi-
ronmental factors such as sex, season, oxygen tension, and diet. Improved methodology for the mea-
surement of DNA damage, lipid peroxidation, and other biomarkers of effect will permit more sensitive
assays, and increased knowledge of fish-specific forms of antioxidant enzymes will provide more specific
assays. Further testing of relatively new techniques such as the TOSC assay may lead to powerful new
tools. The development of transgenic fish with reporter genes activated by oxidative stress (Carvan et
al., 2001) may result in highly specific measurements of the generation on ROS in vivo, in the laboratory,
or in the field. Assays that take advantage of fish-specific biology may also prove valuable; for example,
the presence of nucleated blood cells in fish permits a nonlethal measurement of DNA damage (Tiano
et al., 2001; Villarini et al., 1998) as well as other endpoints (Anderson, 1994; Bainy et al., 1996;
Gabryelak and Klekot, 1985; Ritola et al., 2002).
At the same time as biochemical and molecular methodologies are improved and mechanistic under-
standing of oxidative stress in aquatic organisms is refined, it will be important to begin to more carefully
explore relationships between exposure to oxidative stress and population-level effects. The associations
between contaminant exposure and cancer epizootics and other fitness costs mentioned above suggest
that oxidative stress is an ecologically important phenomenon; however, few attempts have been made
to quantify the costs of the oxidative damage caused by environmental pollutants for individual fish,
fish populations, and aquatic ecosystems. Although a mechanistic understanding of oxidative stress in
fish is important from the standpoint of comparative toxicology and basic biology, a solid understanding
of the ecological importance of oxidative stress is dependent upon studies of higher level effects.

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