POLLUTION EFFECTS ON FISH 1013
excretable by the kidney. Without these biotransformations,
the effects of some foreign substances on organisms would
last for months (Brodie et al., 1965). Excretion of these lipid-
insoluble metabolites can be achieved by active secretion at
the tubules of the kidney or by passive transport across the
glomerular membrane into the renal tubule (Forster, 1961,
1967). Since the metabolite has been transformed to a less
lipid-soluble derivative, it will not diffuse back into the
plasma for recirculation subsequent to passing through the
glomerulus into the tubule.
The microsomal enzymes were, until recently, thought
to be concerned only with the metabolism of compounds
which are normally regarded as foreign to the body. Conney
(1967) has recently shown that steroid hormones and other
normal body constituents are also substrates of the drug-
metabolizing enzymes in liver microsomes and he suggests
that this enzyme system may play a significant role in their
regulation and physiological action. These enzyme systems
are thought to operate by a mixed function oxidase mecha-
nism whereby NADPH reduces a component in microsomes
which reacts with molecular oxygen to form an “active
oxygen” intermediate. The “active oxygen” is then trans-
ferred to the drug or toxicant (Gillette, 1963). Key enzymes
in the overall reaction are NADP-cytochrome c reductase,
the flavin enzyme involved in the oxidation of NADP, cyto-
chrome P-450, and NADPH cyctochrome P-450 reductase,
which acts to reduce oxidized cytochrome P-450 (Gillette
and Sasame, 1966).
Many foreign compounds can alter these key enzymes
and enhance or impair the ability of liver microsomal
enzymes to metabolize other foreign compounds and ste-
roids (Conney, 1967). Halogenated hydrocarbon insecti-
cides have long been known to be potent stimulators of
mammalian drug-metabolizing enzymes (Hart and Fouts,
1963; Hart, Shultice and Fouts, 1963). Buhler (1966)
selectively induced drug-metabolizing enzymes in rain-
bow trout by exposing these animals to DDT or phenyl-
butazone. Organophosphate insecticides are unlike the
halogenated hydrocarbons in that they inhibit, rather than
stimulate, the metabolism of drugs and steroids by liver
microsomes, when given chronically to rats (Rosenberg
and Coon, 1958; Welch et al., 1967). Some heavy metals
(Fe^ ^ , Cu^ , Zn^ ^ and Co^ ^ ) have also been shown to be
inhibitory to drug metabolism in mice and rats (Peters
and Fouts, 1970). Alterations in microsomal enzyme
metabolizing capacities can substantially alter an animal’s
response to foreign compounds as well as its ability to
hydroxylate steroid hormones and other normal body con-
stituents (Conney, 1967). Altered steroid metabolism can
directly affect the animal’s ability to cope with environ-
mental stresses as well as seriously impair reproductive
mechanisms.
Other than Buhler’s (1966) work on rainbow trout,
little is known about the effects foreign compounds have
on the microsomal drug metabolizing capacities of fishes.
In addition, the current state of knowledge dealing with
metabolism of foreign compounds in fishes is, at best,
scanty (Adamson, 1967).THE TOXICITY OF COMPLEX EFFLUENTSMost industrial effluents contain mixtures of two or more
substances. These complex effluents present special prob-
lems in evaluating their toxicities to fish and other organisms.
In some cases two agents with similar pharmacologic actions
can produce a response that is equal to the summation of the
effects of the individual agents or greater than the summa-
tion of the independent effects of the two agents. The latter
response is called “potentiation” and represents the condition
whereby one compound is made more toxic in the presence of
another compound which alone may produce minimal or no
pharmacologic effect. Potentiation poses a special problem
for the aquatic environment as well as the terrestrial environ-
ment for it is possible that a certain combination of relatively
harmless substances may result in an unpredictable high level
of toxicity that would seriously threaten the existence of one
or many species. Usually, however, the effect of two agents
is the summation of responses to each agent. Occasionally,
the effect of a toxic substance is reduced on the addition of
another substance, a phenomenon referred to as antagonism.
In some cases the antagonistic substance may or may not be
toxic when present by itself.
Synergism (potentiation and summation) and antagonism
are poorly understood phenomena and greatly confuse the
understanding and prediction of the toxic effects of industrial
effluents. The majority of toxicological studies conducted in
this and other countries on both mammals and fish deal with
the effects of single substances on organisms; only a few stud-
ies are currently investigating the responses of organisms to
complex mixtures of substances. Synergism and antagonism
are worthy of further investigation, for little is known about
the basic mechanisms governing these processes.RESISTANCE OF FISH TO TOXICANTSResistance of animals to chemicals has been known to exist
for some time now and has posed serious obstacles in the
control of insects and bacteria. While the mechanisms of
resistance remain thus far a mystery, we know that they are
genetically based. Most susceptible populations of animals
have an occasional individual which exhibits resistance and
it is this member that provides the genetic material for selec-
tion pressures to act upon.
Resistance has best been demonstrated with various
pesticides in several natural populations of fishes (Ferguson
et al., 1964, 1966), but these findings have attracted little
attention. Many biologists have, in fact, believed this phe-
nomenon to be beneficial to these animals, especially since
they are useful to man.
Recently, some disturbing evidence has emerged sug-
gesting that pesticide-resistant vertebrates pose a major
hazard in natural ecosystems and that they may be creating
serious toxicological problems for man (Ferguson, 1967).
The reason for this is some resistant animals carry massive
residues of unaltered pesticides in their tissues and aggra-
vate the already serious problem of biological magnification.C016_009_r03.indd 1013C016_009_r03.indd 1013 11/18/2005 1:12:30 PM11/18/2005 1:12:30 P