Page 202 - The Toxicology of Fishes

182 The Toxicology of Fishes

O
O CNHMe
OH

+ HOOCNHMe

Carbaryl 1-Naphthol

FIGURE 4.6 Reactions catalyzed by carboxylesterases.

activity formed proportionally more of the phenolic rearrangement product, 9-hydroxy-BaP, than BaP-9,10-
dihydrodiol; individuals with high epoxide hydrolase activity formed proportionally more BaP-9,10-dihy-
drodiol and less of the phenolic rearrangement product. This relationship was not found for the ratio of
BaP-7,8-dihydrodiol to 7-hydroxy-BaP. It was thought that this was because of differences in the chemical
reactivity of the arene oxides of BaP. BaP-9,10-oxide, unlike BaP-7,8-oxide, was not readily hydrolyzed
in the absence of epoxide hydrolase, making the presence of the epoxide hydrolase enzyme critical to
determining if BaP-9,10-oxide would be hydrolyzed to the dihydrodiol or rearrange to the 9-hydroxy
product. The presence of compounds that modulate enzyme activity was found to influence the metabolites
of BaP formed in hepatic microsomes from control or 3-methylcholanthrene-induced sheepshead (Little
et al., 1981). Incubation of BaP with hepatic microsomes in the presence of naphthoimidazole, a substance
that inhibits CYP1A but stimulates epoxide hydrolase, gave a higher ratio of BaP-9,10-dihydrodiol to
9-hydroxy-BaP than incubations in the absence of the modulating agent, presumably by routing the
BaP-9,10-oxide formed by CYP1A to BaP-9,10-dihydrodiol rather than to 9-hydroxy-BaP.
Modulation of epoxide hydrolase activity has been investigated following treatment with various
xenobiotics. In mammalian species, several xenobiotics induce epoxide hydrolase activity, including
phenobarbital, trans-stilbene oxide, and some aryl hydrocarbon receptor agonists, including PCBs
(Bresnick et al., 1977; Gillette et al., 1987). In fish, however, induction of epoxide hydrolase activity
following administration of these agents has not been demonstrated (James and Little, 1981; James et
al., 1997). Indeed, in stingrays treated with 3-methylcholanthrene at a dose that induced AHH activity
tenfold, epoxide hydrolase activity was significantly lower in hepatic microsomes from treated fish (4.54
± 0.55 nmol/min/mg protein) relative to controls (5.81 ± 0.76) (James and Bend, 1980). A similar trend
was observed in 3-MC-treated sheepshead. Flatfish exposed to PAH- and PCB-contaminated Puget Sound
sediments showed no increase in epoxide hydrolase activity (Collier and Varanasi, 1991; Collier et al.,
1986). Likewise, channel catfish and brown bullhead treated with 10 mg/kg benzo(a)pyrene showed no
significant induction or species difference in liver microsomal cis-stilbene-oxide hydrolase activities
(Willett et al., 2000). In the splake, treatment with the fish anesthetic tricaine methane sulfonate reduced
epoxide hydrolase activity in liver and duodenum (Laitenen et al., 1981).

Carboxylesterases
Hydrolytic biotransformation of xenobiotics by various forms of carboxylesterases in fish plays a significant
role in the detoxification of various pesticides (Glickman et al., 1982; Straus and Chambers, 1995; Wallace
and Dargan, 1987) and plasticizers (Barron et al., 1989) (Figure 4.6). Most of the studies examining this
pathway in fish have focused on postmitochondrial or cytosolic enzymes (Salamastrakis and Haritos, 1988),
and some studies have examined the microsomal activities (Soldano et al., 1992; Vittozzi et al., 2001). No
carboxylesterase genes have been characterized in fish, but studies with purified proteins (e.g., chlorpyrifos)
have been carried out (Boone and Chambers, 1997). Differences in carboxylesterase activities among
species have been hypothesized to be responsible for the acute toxicity of organophosphates (Keizer et al.,
1991, 1993, 1995) and pyrethroids (Glickman et al., 1979, 1982). Carp were resistant to diazinon toxicity
because of relatively high activity of hydrolyzing esterase activity, whereas trout was very sensitive to
toxicity because of a lack of esterase activity and a sensitive acetylcholinesterase (Keizer et al., 1995). A
similar relationship was observed in trout with permethrin (Glickman et al., 1979).