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

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AX5-104<br />

Table AX5-6.18. Genotoxic/Carcinogenic Effects <strong>of</strong> <strong>Lead</strong>—Mitogenesis—Animal<br />

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

Pb acetate Administered Pb acetate (12.5 mg/kg) i.p.<br />

Animals studied 24 h after injection.<br />

Pb nitrate Liver initiation induced by the resistant hepatocyte<br />

model<br />

Initiation followed by i.v. injection <strong>of</strong> Pb nitrate<br />

(100 µM/kg ) or partial hepatectomy<br />

Studied DNA synthesis (30 h after injection) and<br />

preneoplastic nodule <strong>for</strong>mation<br />

(5 wks after injection)<br />

Pb nitrate Liver initiation induced by the resistant hepatocyte<br />

model (diethylnitrosamine followed by 2acetylamin<strong>of</strong>luorene<br />

plus carbon tetrachloride)<br />

Initiation followed by i.v. injection <strong>of</strong> 4 doses <strong>of</strong> Pb<br />

nitrate (100 µM/kg ) given once every 20 days or<br />

partial hepatectomy, ethylene dibromide, or<br />

nafenopine<br />

Animal were evaluated <strong>for</strong> preneoplastic foci at 75 or<br />

155 days after initiation.<br />

Pb nitrate Liver initiation induced by the orotic acid model<br />

(diethylnitrosamine plus orotic acid)<br />

Initiation followed by i.v. injection <strong>of</strong> Pb nitrate<br />

(100 µM/kg) or partial hepatectomy, or by gavage:<br />

ethylene dibromide, or cyproterone<br />

DNA synthesis was examined at various time<br />

intervals (24 h–5 days) after injection.<br />

Male B6 Mice None Pb acetate induced TNF-alpha in glial and<br />

neuronal cells in the cerebral cortex and<br />

subcortical white matter and on Purkinje cells in<br />

the cerebellum, but did not induced apoptosis in<br />

these areas<br />

Male Wistar<br />

Rats—4 per group<br />

Male Wistar<br />

Rats—4 per group<br />

Male Wistar<br />

Rats—4 per group<br />

Partial Hepatectomy Pb nitrate stimulated DNA synthesis and liver cell<br />

proliferation<br />

Pb nitrate did not induce preneoplastic nodule.<br />

Partial hepatectomy did.<br />

Diethylnitrosamine Pb nitrate, partial hepatectomy, ethylene<br />

dibromide, or nafenopine all stimulated DNA<br />

synthesis and liver cell proliferation<br />

Pb nitrate, ethylene dibromide, or nafenopine did<br />

not induce preneoplastic nodule. Partial<br />

hepatectomy did.<br />

Diethylnitrosamine Pb nitrate, partial hepatectomy, ethylene<br />

dibromide, or cyproterone all stimulated DNA<br />

synthesis within 30 min.<br />

Pb nitrate induced DNA synthesis <strong>for</strong> 5 days.<br />

Cheng et al. (2002)<br />

Columbano et al.<br />

(1987)<br />

Columbano et al.<br />

(1990)<br />

Coni et al. (1992)

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