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

AX5-101
Compound
Table AX5-6.15. Genotoxic/Carcinogenic Effects of Lead—Epigenetic Effects and Mixture Interactions—Human
Assay (Concentration and
Exposure Time)
Pb acetate Tyrosine aminotransferase
expression and activity
(0.3–10 µM for 24–48 h)
PKC activity: 10 µM for 48 h
Pb nitrate EROD/MROD activity
(10–100 µM for 24 h)
NAD(P)H: quinone
oxidoreductase activity
(10–100 µM for 24 h)
Glutathione-S-transferase
Ya activity (10–100 µM for 24 h)
Pb nitrate NAD(P)H: quinone
oxidoreductase activity
(25 µM for 24 h)
Glutathione-S-transferase Ya
activity (25 µM for 24 h)
Abbreviations
Medium and Components
DMEM—Dulbecco’s Minimal Essential Medium;
FBS—Fetal Bovine Serum
FCS—Fetal Calf Serum
Cell Type
and Culture
Medium Co-exposure Effects Reference
H4-IIE-C3—
human
hepatoma cells
in DMEM +
2.5% FCS
Hepa 1c1c7
wild type cells
in DMEM +
10% FBS
C12- AHRdeficient
Hepa
1c1c7 cells in
DMEM + 10%
FBS
Dexamethasone
(0.1 µM for 16 h),
or calcium chloride
(10 µM) or genistein
(100 µM to block PKC
activity)
TCDD (0.1 nM),
3-methyl cholanthrene
(0.25 µM), betanaptflavone
(10 µM),
benzo(a)pyrene (1 µM)
TCDD (0.1 nM),
3-methyl cholanthrene
(0.25 µM), betanaptflavone
(10 µM),
benzo(a)pyrene (1 µM)
Differences between the serum types are unclear as insufficient details are provided by authors to distinguish.
Pb acetate inhibited glucocorticoid –induction of tyrosine
aminotransferase in a time- and dose-dependent manner.
Co-treatment with calcium reduced the effects of Pb.
Co-treatment with genistein increased the effects of Pb.
Pb acetate decreases PKC activity and its translocation from the
cytosol to the particulate cellular fraction.
Pb did not affect EROD/MROD activity.
Pb reduced CYP1A1 induction by TCDD, 3-methyl cholanthrene,
beta-naptflavone, benzo(a)pyrene.
Pb increased NAD(P)H: quinone oxidoreductase activity
Pb increased NAD(P)H: quinone oxidoreductase activity induction by
TCDD, 3-methyl cholanthrene, beta-naptflavone, benzo(a)pyrene.
10 µM increased Glutathione-S-transferase Ya activity.
25 and 100 µM increased Glutathione-S-transferase Ya activity.
Pb nitrate did not affect Glutathione-S-transferase Ya induction by
TCDD, 3-methyl cholanthrene, beta-naptflavone, benzo(a)pyrene.
Pb nitrate did not increase NAD(P)H: quinone oxidoreductase and
Glutathione-S-transferase Ya activity
Pb increased NAD(P)H: quinone oxidoreductase activity induction by
TCDD, 3-methyl cholanthrene, beta-naptflavone, benzo(a)pyrene.
Pb did not affect Glutathione-S-transferase Ya induction by TCDD, 3methyl
cholanthrene, beta-naptflavone, benzo(a)pyrene.
Tonner and Heiman
(1997)
Korashy and
El-Kadi (2004)
Korashy and
El Kadi (2004)