Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout
Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout
Date
2011-04-08
Authors
Curtis, Lawrence R.
Garzon, Claudia B.
Arkoosh, Mary
Collier, Tracy K.
Myers, Mark S.
Buzitis, Jon
Hahn, Mark E.
Garzon, Claudia B.
Arkoosh, Mary
Collier, Tracy K.
Myers, Mark S.
Buzitis, Jon
Hahn, Mark E.
Linked Authors
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Person
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Location
DOI
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Keywords
Cytochrome P4501A activity
Oxidative stress
Benzo[a]pyrene
Benzo[e]pyrene
Aryl hydrocarbon receptor
Biliary excretion
Fish
Oxidative stress
Benzo[a]pyrene
Benzo[e]pyrene
Aryl hydrocarbon receptor
Biliary excretion
Fish
Abstract
This
study
assessed
the
role
of
aryl
hydrocarbon
receptor
(AHR)
affinity,
and
cytochrome
P4501A
(CYP1A)
protein
and
activity
in
polyaromatic
hydrocarbon
(PAH)-‐induced
oxidative
stress.
In
the
1-‐100
nM
concentration
range
benzo[a]pyrene
(BaP)
but
not
benzo[e]pyrene
(BeP)
competitively
displaced
2
nM
[3H]2,
3,
7,
8-‐tetrachloro-‐dibenzo-‐p-‐dioxin
from
rainbow
trout
AHR2α.
Based
on
appearance
of
fluorescent
aromatic
compounds
in
bile
over
3,
7,
14,
28
or
50
days
of
feeding
3
μg
of
BaP
or
BeP/g
fish/day,
rainbow
trout
liver
readily
excreted
these
polyaromatic
hydrocarbons
(PAHs)
and
their
metabolites
at
near
steady
state
rates.
CYP1A
proteins
catalyzed
more
than
98%
of
ethoxyresorufin-‐O-‐deethylase
(EROD)
activity
in
rainbow
trout
hepatic
microsomes.
EROD
activity
of
hepatic
microsomes
initially
increased
and
then
decreased
to
control
activities
after
50
days
of
feeding
both
PAHs.
Immunohistochemistry
of
liver
confirmed
CYP1A
protein
increased
in
fish
fed
both
PAHs
after
3
days
and
remained
elevated
for
up
to
28
days.
Neither
BaP
nor
BeP
increased
hepatic
DNA
adduct
concentrations
at
any
time
up
to
50
days
of
feeding
these
PAHs.
Comet
assays
of
blood
cells
demonstrated
marked
DNA
damage
after
14
days
of
feeding
both
PAHs
that
was
not
significant
after
50
days.
There
was
a
strong
positive
correlation
between
hepatic
EROD
activity
and
DNA
damage
in
blood
cells
over
time
for
both
PAHs.
Neither
CYP1A
protein
nor
3-‐
nitrotyrosine
(a
biomarker
for
oxidative
stress)
immunostaining
in
trunk
kidney
were
significantly
altered
by
BaP
or
BeP
after
3,
7,
14,
or
28
days.
There
was
no
clear
association
between
AHR2α
affinity
and
BaP
and
BeP-‐induced
oxidative
stress.
Description
Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Toxicology and Applied Pharmacology 254 (2011): 1-7, doi:10.1016/j.taap.2011.04.015.