Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

AX5-160
Table AX5-10.1 (cont’d). Hepatic Drug Metabolism
Concentration Duration Species Blood Lead Effects a Reference
Pb nitrate,
100 µm/kg i.p,
3 times every 24 h
Pb acetate
100 µM/kg.
10 nM Pb nitrate 24 h before
transfection with
ECAT deletion
mutant, every 24
h there after till
48 h after
transfection
10 mg Triethyl Pb,
i.p. single dose
114 mg Pb
acetate/kg b. wt. i.p
A. 1.5–3.0 mg/kg
wt
Triethyl Pb (TEL)
i.p.
B. 0.05–0.5, TEL
to liver microsomal
fractions
48 h Transgenic rats
with 5 different
constructs
—
0.5–24 h
having GST-P
and/or
chloromphenica
l acetyl
transferase
coding
sequence.
—
Analyses at
multiple durations
(3, 4, 7, 10, or 14
days)
Single (0.5–12 h
group) or multiple
(72 h and 7 days
group) exposure
2 exposures for
48 h
30 min
incubations
NRK Kidney
fibroblasts
GSTP (placental GST), is regulated by Pb at transcriptional level.
GST-P enhancer (GPEI), is an essential cis-element required for the
activation of the GST-P gene by Pb and is involved in the activation
regardless of the trans-activators involved. GPEI element consists
of two AP-1 binding sites. Activation of GST-P gene by Pb is
mediated in major part by enhancer GPEI, which may involve AP-1
activation partially.
— Pb induces GST-P in NRK normal rat kidney fibroblast cell line.
Fischer 344 rats — Decreased liver Glutathione s-transferase (GST) activity and lower
levels of several hepatic GST.
Increase in quinone reductase activity by day 14 in liver.
Sprague Dawley — Pb exposure resulted in hepatic Glutathione (GSH) depletion and
increased malondialdehyde (MDA) production.
Female Wistar — Pretreatment of rats did not affect the liver microsomal Oestradiol-
17β metabolism or the content of cytochrome P-450 and
cytochrome b5.
Liver
microsomes
from female
Wistar rats
— TEL at 0.05 mM significantly reduced 17β-hydroxy steroid
oxidation and at concentration of 0.05 mM decreased 16αhydroxylation.
Suzuki et al.
(1996)
Daggett et al.
(1997)
Daggett et al.
(1998)
Odenbro and
Rafter (1988)