previously, but also ozone (O 3 ), CCl 4 , and organophosphorus insecticides. The
consequence of the actions of these chemicals on microsomal enzymes is
complex and may include normal body constituents, such as steroid hormones,
thyroxin, and bilirubin, or altered metabolism and action of drugs and
carcinogens.
The health status of an individual, including nutritional status, also plays
an important role in biotransformation. As noted earlier, several endogenous
substances, such as glycine, glutamine, glucuronic acid, and GSH are necessary
for conjugation with xenobiotics or their metabolites in Phase II biotransformation (Figure 6.3). Glycine and glutamine are both amino acids, GSH is a
tripeptide derived from three amino acids, and glucuronic acid is formed from
glucose that is derived directly from dietary source or derived from liver
glycogen through glycogenolysis (breakdown of glycogen). It is therefore likely
that the availability of proteins or liver reserves of glycogen may be insufficient
in individuals with poor nutritional status or liver problems. These conditions
can lead to impaired biotransformation.
The importance of ethoxyresorufin O-deethylase (EROD), one of the
hepatic cytochrome P450-dependent mono-oxygenases, has become widely
known, and is increasingly accepted as an indicator of exposure to common
organic pollutants. Various organic chemicals, including chlorinated hydrocarbons, have been shown to adversely affect the enzymes involved in
biotransformation. This is manifested in a study summarized in Case Study
6.1. The results in Case Study 6.1 suggest that pollutants such as PCBs may
activate detoxification capacity, but weaken antioxidant status, in fish in a
polluted river system.
7
CASE STUDY 6.1
A group of researchers collected brown bullheads (Ameiurus nebulosus) from the
St. Lawrence River, a relatively polluted system, and compared various
parameters in the fish with those in fish from Lac La Peche, a relatively nonpolluted system in Canada (used as a reference).
7 The main results obtained
were as below:
The activities of liver ethoxyresorufin O-deethylase (EROD) À a common
Phase I enzyme À in fish collected from the St. Lawrence River were
significantly higher (2.8-fold) than those in fish from the reference site.
The conjugation activity by hepatic glutathione S-transferase (GST) was
three times higher in fish from the St. Lawrence River than in fish from the
reference site.
The content of PCBs in white muscle was 22 times higher in fish from the St.
Lawrence River than in fish from the reference site.
The activities of cytosolic SOD were significantly higher, while those of
catalase in kidney and GSHPx in red and white muscles were lower, in the
St. Lawrence River fish than those in the reference fish.
The concentrations of total GSH in different tissues were significantly lower
in liver, kidney, and white muscle of fish from the St. Lawrence River
compared with those in fish from the reference site.
94
Environmental Toxicology
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Ref: 4365 MING-HO YU Chap-006 Page: 94 85-98
consequence of the actions of these chemicals on microsomal enzymes is
complex and may include normal body constituents, such as steroid hormones,
thyroxin, and bilirubin, or altered metabolism and action of drugs and
carcinogens.
The health status of an individual, including nutritional status, also plays
an important role in biotransformation. As noted earlier, several endogenous
substances, such as glycine, glutamine, glucuronic acid, and GSH are necessary
for conjugation with xenobiotics or their metabolites in Phase II biotransformation (Figure 6.3). Glycine and glutamine are both amino acids, GSH is a
tripeptide derived from three amino acids, and glucuronic acid is formed from
glucose that is derived directly from dietary source or derived from liver
glycogen through glycogenolysis (breakdown of glycogen). It is therefore likely
that the availability of proteins or liver reserves of glycogen may be insufficient
in individuals with poor nutritional status or liver problems. These conditions
can lead to impaired biotransformation.
The importance of ethoxyresorufin O-deethylase (EROD), one of the
hepatic cytochrome P450-dependent mono-oxygenases, has become widely
known, and is increasingly accepted as an indicator of exposure to common
organic pollutants. Various organic chemicals, including chlorinated hydrocarbons, have been shown to adversely affect the enzymes involved in
biotransformation. This is manifested in a study summarized in Case Study
6.1. The results in Case Study 6.1 suggest that pollutants such as PCBs may
activate detoxification capacity, but weaken antioxidant status, in fish in a
polluted river system.
7
CASE STUDY 6.1
A group of researchers collected brown bullheads (Ameiurus nebulosus) from the
St. Lawrence River, a relatively polluted system, and compared various
parameters in the fish with those in fish from Lac La Peche, a relatively nonpolluted system in Canada (used as a reference).
7 The main results obtained
were as below:
The activities of liver ethoxyresorufin O-deethylase (EROD) À a common
Phase I enzyme À in fish collected from the St. Lawrence River were
significantly higher (2.8-fold) than those in fish from the reference site.
The conjugation activity by hepatic glutathione S-transferase (GST) was
three times higher in fish from the St. Lawrence River than in fish from the
reference site.
The content of PCBs in white muscle was 22 times higher in fish from the St.
Lawrence River than in fish from the reference site.
The activities of cytosolic SOD were significantly higher, while those of
catalase in kidney and GSHPx in red and white muscles were lower, in the
St. Lawrence River fish than those in the reference fish.
The concentrations of total GSH in different tissues were significantly lower
in liver, kidney, and white muscle of fish from the St. Lawrence River
compared with those in fish from the reference site.
94
Environmental Toxicology
[16:54 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-006.3d]
Ref: 4365 MING-HO YU Chap-006 Page: 94 85-98