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

AX5-176
Table AX5-10.5 (cont’d). Lead-induced Liver Hyperplasia: Mediators and Molecular Mechanisms
Concentration Duration Species Blood Lead Effects a Reference
Pb (No3)2, , i.v.
100 µM/110 g .b. wt
GdCl3
0.75 mg/100 g. b. wt,
i.v.
In vitro, 10 mM Pb
nitrate
Multiple
concentrations
varying from
300 nM–10 µM,
up to 100 µM in
certain in vitro expts
0–10 µM Pb acetate
in the culture medium
a CYP—Cytochrome P-450
b. wt.—body weight
1, 3, and 5 days In vivo Adult
male Wistar rats
2, 4, or 24 h before Pb
nitrate injection.
Analyses at multiple
time points up to 24 h
in Hep G2 cells and at
24 and 48 h in
Kupffer cells
1, 2, 4 and 6 days Hepatoma cell
line, H4-II-C3
24 and 48 h H4-IIE—C3
hepatoma cell
culture model
—
—
Hep G2 cells —
Hepatic apoptosis induced by Pb nitrate in vivo is abolished by gadolium
chloride, a Kupffer cell toxicant that suppresses Kupffer cell activity and
reduces to half the apoptotic rate. Pb nitrate treatment also deprives the
hepatic cells from reduced glutathione and this process is reversed by
Gadolium chloride. Pb nitrate induces apoptosis in Kupffer cells, and
HepG2 cells in vitro.
— Acute effect of Pb on glucocorticoid regulation of Tyrosine
aminotransferase (TAT) in hepatoma cells. Pb treatment does not
significantly alter initial glucocorticoid receptor number or ligand binding.
Pb may perturb PKC mediated phosphorylations in the glucocorticoid-
TAT signal transduction system. Pb also may be increasing the turnover
of TAT by actions at transcription, translation and /or post translation.
— In HTC cells glucocarticoid signal transduction pathways involve calcium-
mediated events and PKC isoforms, Pb exposure interferes with calcium
mediated events and aberrant modulation of PKC activities and may
contribute to the over all toxicity of Pb.
Pagliara (2003b)
Heiman and Toner
(1995)
Tonner and Heiman,
(1997)