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

AX5-107
Compound
Table AX5-6.19. Genotoxic/Carcinogenic Effects of Lead—Mitogenesis Human and Animal Cell Culture Studies
Assay (Concentration and
Exposure Time)
Pb acetate Cell Proliferation (0.1–100 µM for
2–6 days)
DNA synthesis (1–100 µM for
72 h)
Tyrosine aminotransferase
expression and activity (0.3–10 µM
for 24– 48 h)
Pb acetate Cell proliferation (10 µM–1mM for
24 h–7 days)
Pb acetate Cell growth (0.01–10 µM for
12-72 h)
Expression of genes in cytokine
pathways (0.01–10 µM for 24 h)
Pb acetate Cell proliferation (0.078–320 µM
for 48 h)
Apoptosis (1.25–80 µM)
Cell cycle analysis
Pb acetate DNA synthesis (1–50 µM for 24 h)
Expression of genes in mitogen
activated pathways (1–50 µM for
5 min–4 h)
Pb acetate Cell proliferation (1 µM for 24 h)
Cell differentiation
(1 µM for 48 h)
PKC activation (1 µM for 24 h)
Cell Type and
Culture Medium Co-exposure Effects Reference
H4-II-C3—human
hepatoma cells in DMEM
+ 2.5% FCS
REL cells—Rat Epithelial
cells in Ham’s F10
medium + 10% FBS
U-373MG—human
glioma cell line in DMEM
+ 10 or 20% FBS
Rat-1 fibroblasts in
EMEM +10% FBS
1321N1–human
astrocytoma cells in
DMEM + 0.1% BSA
Primary oligodendrocyte
progenitor cells–in
DMEM + 1% FBS
Dexamethasone
(0.1 µM for 16 h)
Pb acetate inhibited cell growth in a time- and dosedependent
manner.
Pb acetate inhibited DNA synthesis in a dose-dependent
manner.
Pb acetate alone did not inhibit tyrosine aminotransferase.
Pb acetate inhibited glucocorticoid–induction of tyrosine
aminotransferase in a time- and dose-dependent manner.
None Pb acetate inhibited cell growth at all concentrations for
24 h–7 days.
Pb acetate did not affect gap junction capacity, which is
often inhibited by tumor promoters.
None Pb acetate did not inhibit or enhance cell growth.
Pb acetate enhanced the expression of TNF-alpha, but
decreased interleukin-1 beta, interleukin-6, gammaaminobutyric
acid transaminase, and glutamine synthetase
under 10% FBS.
Pb acetate further enhanced the expression of TNF-alpha
under 20% serum, but had no effect at all on expression of
the other genes.
None Pb acetate inhibited cell growth at 0.635–320 µM.
Pb acetate induced apoptosis from 2.5–10 µM.
Pb acetate caused GS/M and S-phase arrest.
None Pb acetate induced DNA synthesis.
Pb acetate induced activation of MAPK, ERK1. ERK2,
MEK1 , MEK2, PKC, and p90 RSK .
Pb acetate did not activate PI3K or p70 s6k .
None Pb acetate inhibited basal and growth factor stimulated
growth.
Pb acetate inhibited cell differentiation in a PHC-dependent
manner.
Pb acetate redistributes PKC from the cytosol to the
membrane, but did not increase PKC activity.
Heiman and
Tonner (1995)
Apostoli et al.
(2000)
Liu et al. (2000)
Iavicoli et al.,
(2001)
Lu et al. (2002)
Deng and Poretz
(2002)