Page 618 - The Toxicology of Fishes

598 The Toxicology of Fishes

Introduction
Chemical Tolerance or Resistance to Toxic Effects

Although chemical contamination of our environment is often associated with human activities, plants
and animals have evolved in an environment that has included continuous exposure to toxic materials
(Ames et al., 1990a,b; Gribble, 1994; Menzie et al., 1992; Shaw, 1999). Basic mechanisms for resisting
toxicity probably evolved with early life and are likely to be highly conserved in nature (Borst, 1993;
Doehmer et al., 1993; Doige and Ames, 1993; Gonzales and Nebert, 1990; Gottesman and Pastan, 1993;
Hayes and Pulford, 1995; Nebert et al., 1990; Roesjadi, 1992; Sheehan et al., 2001). Because of the
large number and wide distribution of novel anthopogenic compounds introduced into the modern world,
these mechanisms have become increasingly essential for survival. Organisms surviving environments
heavily contaminated with anthropogenic chemicals demonstrate a diversity of mechanisms to tolerate
or resist toxic effects.
Resistance or tolerance can be defined as the relative ability to function or survive during toxicant
exposures that are harmful or lethal to susceptible individuals and populations. In the laboratory, tolerance
is confirmed when chemical exposures that are toxic to individuals from uncontaminated sites are less
toxic to individuals with a history of chemical exposure.
Fish and other organisms appear to develop tolerance through a variety of short-term and long-term
processes (Benson and Birge, 1985; Chambers and Yarbrough, 1979; Chevillon et al., 1997; Doehmer
et al., 1993; Eaton and Bammler, 1989; Fernandez-Salguerro et al., 1996; Kurelec, 1992; Taylor and
Feyereisen, 1996; Roesjadi, 1992; Winston, 1991; Winston and Di Giulio, 1991). Physiological acclima-
tion and genetic adaptation are general terms for short-term, transitory responses and long-term, heritable
responses, respectively (Table 13.1). Physiological acclimations occur in direct response to toxic expo-
sures and likely involve temporary alterations in the levels of expression of proteins and enzymes involved
in chemical defense. Following chemical exposure, protein expression returns to normal and the state of
physiological acclimation declines. Genetic adaptation or evolved tolerance occurs when the genetic basis
for advantageous responses is passed on to progeny. In genetic adaptation, tolerance is retained through
successive generations, even when progeny are not exposed to chemicals (Endler, 1986).
The terms physiological acclimation and genetic adaptation have been used frequently for categorizing
mechanisms of chemical tolerance in fish (Elskus, 2001; Hahn, 1998; Weis and Weis, 1989; Wirgin and
Waldman, 1998, 2004); however, other processes and conditions may contribute to tolerance as well
(Table 13.1). For example, abundant evidence indicates that some forms of chemically induced cancer

TABLE 13.1
Processes and Conditions Contributing to Resistance
Type of Resistance Description
Resistance or tolerance Relative ability of individuals or populations to function or survive during
toxicant exposures that is inhibitory or lethal to susceptible (sensitive)
individuals or populations of the same species
Physiological acclimation Resistance based on short-term physiological or biochemical responses to
toxicant exposure (e.g., induction of biotransformation enzyme)
Genetic adaptation (evolved tolerance) Resistance that is passed onto progeny and retained through successive
generations; likely involves genetic alterations in target sites, toxicant
receptors, and proteins involved in detoxification, toxicant binding, and efflux
Cancer Resistance resulting from nonheritable gene mutations and biochemical
alterations that occur during chemical carcinogenesis
Epigenetic alterations Resistance resulting from modifications in DNA (e.g., hypermethylation) that
do not involve mutations in nucleotide sequence but alters (e.g., silences)
gene expression
Nongenetic, heritable tolerance Resistance resulting from maternal transfer of toxicant or mRNA from parent
to offspring; resistance does not likely last beyond one generation