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

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AX5-85<br />

Table AX5-6.5. Genotoxic/Carcinogenic Effects <strong>of</strong> <strong>Lead</strong>—Genotoxicity Human Cell Cultures Mutagenesis<br />

Compound Dose and Duration Cell Type Co-exposure Effects Reference<br />

Pb acetate,<br />

In vitro<br />

Cytotoxicity–tritium<br />

incorporation (0.1–<br />

100 µM/mL <strong>for</strong> 2–24 h)<br />

Mutagenesis–HPRT<br />

modified to labeling <strong>of</strong><br />

6-thioguanine resistant cells<br />

(0.1–100 µM/mL <strong>for</strong><br />

2–24 h)<br />

Pb acetate Cytotoxicity (500–<br />

2,000 µM <strong>for</strong> 24 h)<br />

Mutagenicity–HPRT assay<br />

(500–2,000 µM <strong>for</strong> 24 h)<br />

Pb chromate Mutagenicity as 6thioguanine<br />

resistance<br />

(0.25–1 µM <strong>for</strong> 24 h)<br />

Human Keratinocytes<br />

pooled in MEM and low<br />

calcium MEM + 2% FBS<br />

Human Foreskin<br />

Fibroblasts (Chinese)<br />

in DMEM +10% FCS<br />

Human Foreskin<br />

Fibroblasts<br />

In EMEM +15% FCS<br />

None Decrease in tritium incorporation at 10–100 µM/mL.<br />

6 µM/L was selected as the concentration to study as tritiumincorporation<br />

was highest and greater than control.<br />

Tritium incorporation in the presence <strong>of</strong> 6-thioguanine (TG)<br />

was optimal after 4 h Pb acetate exposure and 5 days <strong>of</strong><br />

expression time. It was concluded that the significant<br />

increase relative to control indicated mutations. The<br />

argument made was that because these cells are TG resistant<br />

they must be mutated. However, this argument was not<br />

proven by sequencing or colony <strong>for</strong>mation in TG.<br />

3-aminotriazole (3-AT)<br />

(80 mM to inhibit<br />

catalase)<br />

Abbreviations<br />

Medium and Components<br />

MEM—Minimal Essential Medium;<br />

DMEM—Dulbecco’s Minimal Essential Medium;<br />

EMEM—Eagle’s Minimal Essential Medium;<br />

FBS—Fetal Bovine Serum<br />

FCS—Fetal Calf Serum<br />

Differences between the serum types are unclear as insufficient details are provided by authors to distinguish.<br />

LC50 = 500 µM. Cytotoxicity not affected by 3-AT.<br />

Pb acetate was not mutagenic.<br />

Mutagenicity not affected by 3-AT.<br />

Ye (1993)<br />

Hwua and Yang<br />

(1998)<br />

None Pb chromate was not mutagenic. Biedermann and<br />

Landolph (1990)

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