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

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AX5-100<br />

Table AX5-6.14. Genotoxic/Carcinogenic Effects <strong>of</strong> <strong>Lead</strong>—Epigenetic Effects and Mixture Interactions—Animal<br />

Compound Exposure Regimen Species Co-exposure Effects Reference<br />

Pb acetate Administered as an i.p. injection <strong>of</strong><br />

100 µl/kg.<br />

Animals were studied either 24 h<br />

after a daily dose <strong>for</strong> 3 days or <strong>for</strong><br />

various times (5 min–48 h) after a<br />

single dose.<br />

Pb nitrate Administered as an i.p. injection <strong>of</strong><br />

100 µmol/kg.<br />

Animals were studied either 24 h<br />

after a daily dose <strong>for</strong> 3 days or <strong>for</strong><br />

various times (5 min–48 h) after a<br />

single dose.<br />

Pb nitrate Administered as an i.p. injection <strong>of</strong><br />

100 µmol/kg. Some rats were<br />

partially hepatectomized.<br />

Animals were studied 48 h after<br />

injection.<br />

Pb nitrate Administered as an i.v. injection <strong>of</strong><br />

20, 50, or 100 µmol/kg.<br />

Animals were studied 24 h after<br />

injection.<br />

Male Wistar Rats—<br />

10 wks old<br />

Male Wistar Rats—<br />

10 wks old<br />

Male Sprague<br />

Dawley rats<br />

Male Fisher 344<br />

rats—7 wks old<br />

Actinomycin D<br />

(0.8 mg/kg)<br />

administered i.p. <strong>for</strong><br />

4 h be<strong>for</strong>e a single<br />

dose <strong>of</strong> Pb acetate.<br />

Actinomycin D<br />

(0.8 mg/kg)<br />

administered i.p. <strong>for</strong><br />

4 h be<strong>for</strong>e a single<br />

dose <strong>of</strong> Pb acetate.<br />

Pb acetate induced GST-P, which required the cis element, GPEI<br />

(GST-P enhancer I).<br />

Actinomycin D blocked the effects indicating that regulation was<br />

at the mRNA level.<br />

Pb acetate induced c-jun, which exhibited three peaks <strong>of</strong> exposure<br />

over 48 h.<br />

Pb acetate was more potent than Pb nitrate.<br />

Pb nitrate induced GST-P, which required the cis element, GPEI<br />

(GST-P enhancer I).<br />

Actinomycin D blocked the effects indicating that regulation was<br />

the mRNA level.<br />

Pb nitrate induced c-jun, which exhibited three peaks <strong>of</strong> exposure<br />

over 48 h.<br />

Pb nitrate was less potent than Pb acetate.<br />

Partial Hepatectomy Pb nitrate induced GSH and GST 7-7 activity.<br />

Partial hepatectomy did not induce GSH or GST 7-7.<br />

2-methoxy-<br />

4-aminobenzene to<br />

induce P4501A2<br />

or<br />

3-methylcholanthrene<br />

to induce 4501A1<br />

Pb nitrate selectively inhibited P4501A2 and its induction by 2methoxy-4-aminobenzene<br />

at the mRNA and protein level in a<br />

dose-dependent manner.<br />

Pb nitrate had minimal effect on P4501A1 and its induction by 3-<br />

methyl cholanthrene.<br />

Pb nitrate did not affect microsomal activity.<br />

Pb nitrate induced GST-P in a dose-dependent manner.<br />

Suzuki et al.<br />

(1996)<br />

Suzuki et al.<br />

(1996)<br />

Dock (1989)<br />

Degawa et al.<br />

(1993)

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