Chemical Warfare - Organic Pollutants: An Ecotoxicological Perspective - page 10

This argument gains strength from a comparison of monooxygenase activities in
different groups of vertebrates (see Chapter 2, and Walker 1978, Walker 1980, and
Ronis and Walker 1989). Considering the activities of microsomal monooxygenase
toward a range of lipophilic xenobiotics, fish have much lower activities than herbiv-
orous or omnivorous mammals. Among birds, fish-eating birds and other special-
ist predators tend to have much lower activities than omnivorous/herbivorous birds
or mammals (see also Chapter 2, Section 2.3.2.2, and Walker 1998a). Most of the
xenobiotics used in the assays are substrates for enzymes containing P450s belong-
ing to CYP2. It therefore appears that certain P450s (principally CYP2 isoforms)
have evolved in omnivorous/herbivorous vertebrates with adaptation to land, and do
not occur in fish or specialized predatory birds. The fish-eating birds in the study
cannot use diffusion into the water as mechanisms of detoxication to any important
extent; they do not have permeable respiratory membranes, such as the gills of fish,
across which lipophilic compounds can diffuse into ambient water. Also, most of
them spend long periods out of water anyway. It appears that they have not developed
certain P450-based detoxication systems because there have been very few lipophilic
xenobiotics in their food in comparison to the plants eaten by herbivores/omnivores.
There is growing evidence that different P450 forms of families 1 and 2 do have
some degree of specialization, notwithstanding the rather wide range of compounds
that most of them can metabolize. Members of CYP1 specialize in the metabolism of
planar compounds, a characteristic that is due to the structure of the binding sites at
the active center (Chapter 2, and Lewis 1996). CYP1 family can metabolize flavones
and safroles; coumarins are metabolized by CYP2A, pyrazines by CYP2E, and qui-
noline alkaloids by CYP2D. The evolution of P450 forms within the general scenario
of plant-animal warfare is a rich field for investigation.
The extent to which the evolution of defense systems against natural xenobiotics
has been based on alterations in toxicodynamics is an open question. Studies on
the development of resistance by insects to insecticides (see Chapter 2, Section 2.4)
have frequently established the existence of resistant strains possessing insensitive
“aberrant” forms of the target, frequently differing from the normal sensitive forms
by only a single amino acid substitution. Included here are forms of acetylcholines-
terase, axonal sodium channel, and GABA receptor, which are insensitive to organo-
phosphorous insecticides, pyrethroids, and cyclodienes, respectively. This indicates
the existence of considerable genetic diversity in insect populations and the possibil-
ity of the emergence of resistant strains carrying genes coding for insensitive forms
of target proteins under the selective pressure of toxic chemicals. Because at least
two of these targets are common to both human-made insecticides and naturally
occurring ones, it seems probable that resistance of this type evolved in nature long
before the appearance of commercial insecticides.

1.3 toxInS Produced By anImaLS and mIcroorganISmS

1.3.1 T o x i n s p r o d u c e d b y a n i m a l s
Animals use chemical weapons for both defense and attack. Considering defensive
tactics first, bombardier beetles ( Brachinus spp.) can fire a hot solution of irritant