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

AX5-179
Table AX5-10.6 (cont’d). Effect of Lead Exposure on Liver Heme Synthesis
Concentration Duration Species Blood Lead Effects a Reference
Pb acetate, 160 mg/L,
semi liquid diet, oral
Pb acetate,
0.0625 µM–32 µM,
in vitro
1, 5, or 10 mg/kg
b. wt. Pb acetate or
nitrate, i.p.
10 −4 M Pb acetate for
Hep G2 cells
10 mg Pb/kg b. wt. as
Pb acetate , i.p., single
injection
10 and 100 µM Pb
acetate
a CYP—Cytochrome P-450
b. wt = body weight
8 wks Male Wistar rats — Rats exposed to Pb had a higher blood and liver Pb, increased erythrocytic
protoporphyrin. Pb exposure also resulted in hypoactivity of
aminolevulinate dehydrase.
Rats exposed to ethanol and Pb had altered abnormalities in heme similar
to animals exposed to Pb alone.
Hepatic levels of Zn decreased significantly only in animals exposed to
both.
Hepatic GSH, urinary ALA and porphyrin levels were maintained
similarly in all the groups.
Transferrin bound iron uptake by Pb was also inhibited by Pb at higher
concentrations such as 4 µM.
10 min pre incubation
and 20 minute
incubation
3 days
Analyses at multiple
time points up to 72 h
Rabbit
reticulocytes
A. Transgenic
mice carrying
chimeric
human TF
gene
— The effect of Pb on ferrous iron transport is similar between Pb chloride,
acetate, and nitrate and reversible.
Uptake of ferrous iron into all (heme, cytosolic and stromal fractions) was
inhibited by low concentrations of Pb.
50% inhibition in the uptake by cytosol occurred at 1 µM Pb.
— These studies present evidence for the modulation of the synthesis of
human transferrin by Pb. In transgenic mouse with chimeric human
chloromphenical acetyl transferase Pb regulates human Transferrin (TF)
transgenes at the m RNA level. Liver catalase (CAT) enzyme activity,
CAT protein, and TF-CAT m-RNA levels were all suppressed. Pb did not
alter other liver proteins, mouse TF and Albumin.
B. Hep G2 cells — Pb suppressed synthesis of Transferrin protein in cultured human
hepatoma Hep G2 cells.
Transgenic mice
and Hep G 2
cells
— Pb suppresses human transferrin synthesis by a mechanism different from
acute phase response. Common proteins such as C3 and albumin
associated with acute phase response were not altered by Pb. Pb acetate
suppresses 35 S-transferrin protein synthesis and m-RNA levels in Hep G2
cells and transgenic mice, while LPS altered only protein levels.
Santos et al. (1999)
Qian and Morgan
(1990)
Adrian et al. (1993)
Barnum-Huckins
et al. (1997)