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

AX5-157
Table AX5-10.1. Hepatic Drug Metabolism
Concentration Duration Species Blood Lead Effects a Reference
Triethyl Pb
chloride, 0–3.0
mg/kg b. wt.
In vitro, 0.0–3.0
mM triethyl Pb
5 or 10 µmol/100g
b. wt. Pb nitrate;
i.v.
5, 10, 50 mg Pb
acetate kg !1 b. wt.
100 µmol/kg; i.v.
Pb acetate
100 µmol/kg
Pb nitrate; i.v.
100 µmol/kg; i.v.
Pb acetate
100 µmoles /kg;
i.v.
2 days In vitro, rat
microsomes
Not specified In vivo, rat
microsomes
36 h Male Fischer
344 rats
Multiple
durations
(15 days,
2 and 3 mo)
Female albino
rats
24 h Male Fischer
344 rats
9 h before or 6 h
after
2-methoxy-4aminoazobenzene
(2-Meo-AAB)
Male Fischer
344 rats
—
—
Triethyl Pb increased microsomal N-oxygenation in vivo and
decreased microsomal C oxygenation by in vitro treatment. Either
treatment thus gave rise to an increase in the N-oxygenation/Coxygenation
ratio, which may lead to tumor potentiation.
— Pb decreases phase I components (liver microsomal cyt.P-450), and
increases Phase II components (GST, DT diaphorase etc). Liver
cytosol in treated animals had a polypeptide that cross-reacted with
GSTP.
— Over all induction of cyt-p—450 and b5 in liver, long-term increase
in liver GST and GSH.
— Decrease in total CYP amount, selective inhibition of CYP1A2 and
decrease in the expression at m-RNA and protein level, induction of
placental form of glutathione s-transferase (GST-P).
— Male fisher rats treated with different metal ions CPb nitrate, nickel
chloride, cobalt chloride or cadmium chloride exhibited decreased
total CYP amount in liver microsomes. However, only Pb reduced
the levels of the mRNA and protein of CYP 1A2 induced with 2methoxy-4-aminoazobenzene
(2-Meo-AAB) and decreased the
microsomal activity (Per CYP), Pb also induced placental form of
Glutathione, a marker enzyme for preneoplastic lesion.
24 h Male F 344 rats — Inhibition of CYP1A mRNA(s) by Pb nitrate is by aromatic amines,
not by aryl hydrocarbons.
Multiple
durations (3, 6,
12, 24, and 36 h)
Male Wistar
rats
— Stimulation of TNFα preceding hepatocyte DNA synthesis
indicates a role for it in liver cell proliferation.
Pb nitrate enhances sensitivity to bacterial LPS, in hepatocytes.
Odenbro and
Arhenius (1984)
Roomi et al.
(1986)
Nehru and
Kaushal (1992)
Degawa et al.
(1994)
Degawa et al.
(1995)
Degawa et al.
(1996)
Shinozuka et al.
(1994)