Page 707 - The Toxicology of Fishes

Biomarkers 687

Chemical
Tumors
Population
Genetics Protein/Lipid Interaction
Oncogene
suppressor Promoter and coding region Induction
or repression
Mutation Other
Mutation Reproductive toxicities
polymorphisms
impairment
Adducts
Gene
Expression
Genetic
Damage

Apoptosis
FIGURE 16.2 Interrelationships of biochemical biomarkers.

in environmental monitoring is limited by the inability to extrapolate across the levels of biological
organization. The key is the lack of predictability from cause to effect at succeeding levels and the
absence of known linkages between cause and effects between various levels of biological organization.
In many areas of toxicology, without a knowledge of the cause-and-effect relationship, it is not possible
to reliably extrapolate effects between levels of biological organization. Depledge (1994), however,
suggested that the use of ecosystem-level responses also may be misleading with respect to identification
of the cause-and-effect linkage. Schindler (1987) presented an example in which an experimental lake
was artificially acidified, and changes in selected ecological parameters were subsequently followed for
several years following. Alterations in lake transparency were initially attributed to acid effects, but later
analysis indicated that much of the change was due to unusually low rainfall over the period in which
the research was conducted. This provided another example in which correlation was not causation.
Clearly, to avoid misinterpretation of biomarker responses, mechanistic links by which chemical effects
at one level of organization give rise to detrimental effects at higher levels of biological organization
must be established. As an example, alterations in steroid metabolism resulting in changes in hormone
profiles which, in turn, alter sexual behavior and the reproductive competence of a population might
enable prediction of population-level consequences. It is implicit in such an approach that higher order
responses (development and reproduction) would be predicted from measured molecular or cellular level
responses. In the design of biomarker strategies, an integrated approach should be considered in which
a hierarchy of responses are evaluated. The hierarchy can be constructed based on the level of biological
organization that is being monitored or on different degrees of response sensitivity; in fact, as indicated
in Figure 16.1, these hierarchical approaches are parallel.

Biochemical Biomarkers
Alteration of biochemical defense systems is typically the initial response to any toxic insult by a
xenobiotic; hence, measurement of these systems can be extremely sensitive indicators of altered cell
function (Figure 16.2). As discussed above, however, it is imperative that a specific understanding of the
normal homeostatic roles for these mechanisms be achieved prior to their use as indicators of exposure,
effect or susceptibility. For a discussion and listing of biochemical markers, see Stegeman et al. (1992).
For a more thorough discussion of practical uses of biochemical endpoints in aquatic organisms, see