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

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AX5-88<br />

Compound<br />

Table AX5-6.7. Genotoxic/Carcinogenic Effects <strong>of</strong> <strong>Lead</strong>—Genotoxicity Human Cell Cultures DNA Damage<br />

Assay (Concentration and<br />

Exposure Time)<br />

Pb acetate DNA strand breaks as nucleiod<br />

sedimentation (500 µM <strong>for</strong> 20–<br />

25 h)<br />

Pb acetate DNA strand breaks as nucleoid<br />

sedimentation assay (100 µM<br />

<strong>for</strong> 30 min–4 h)<br />

Pb chromate DNA adducts (0.4–0.8 µg/cm 2<br />

<strong>for</strong> 24 h)<br />

Pb chromate DNA double strand breaks<br />

(0.1–5 µg/cm 2 <strong>for</strong> 24 h) by<br />

Comet assay and H2A.X foci<br />

<strong>for</strong>mation<br />

Pb acetate DNA strand breaks and DNA<br />

protein crosslinks and oxidative<br />

lesions by comet assay (1–<br />

100 µM <strong>for</strong> 1 h)<br />

Cell Type and<br />

Culture Medium Co-exposure Effects Reference<br />

HeLa Cells in AMEM<br />

+ 5% FBS<br />

HeLa Cells in<br />

HEPES/<br />

glucose buffer<br />

Primary Human Small<br />

<strong>Air</strong>way Cells in<br />

Clonetics growth<br />

medium<br />

WTHBF-6—human<br />

lung cells with<br />

hTERT in<br />

DMEM/F12 + 15%<br />

CCS<br />

Primary lymphocytes<br />

in RPMI 1640 without<br />

serum<br />

None<br />

See also Table<br />

AX5-6.16<br />

Buthionine<br />

sulfoximine (BSO) to<br />

deplete cells <strong>of</strong> thiols<br />

Pb acetate alone did not induce single strand breaks. Hartwig et al.<br />

(1990)<br />

Pb acetate did not induce DNA strand breaks. Snyder and<br />

Lachmann<br />

(1989)<br />

None Pb chromate induced Pb inclusion bodies and Cr-DNA adducts and<br />

Pb-DNA adducts in a concentration-dependent manner.<br />

None Pb chromate induced DNA double strand breaks in a concentration<br />

dependent manner.<br />

This study showed the damage was due to chromate and not Pb.<br />

Vitamins A (10 µM),<br />

C (10 µM), E<br />

(25 µM), calcium<br />

chloride (100 µM)<br />

magnesium chloride<br />

(100 µM) or zinc<br />

chloride (100 µM)<br />

Pb acetate induced an increase in DNA single strand breaks at 1 µM<br />

that went down with increasing dose. The highest concentration was<br />

significantly less than the damage in untreated controls. For double<br />

strand breaks, all concentrations had more damage than the controls,<br />

but there was less damage in the highest concentrations than the two<br />

lower ones. Pb only induced a slight increase in the amount <strong>of</strong> DNAprotein<br />

crosslinks at the highest concentration.<br />

Co-exposure to magnesium had no effect. Co-exposure to vitamins A,<br />

C, and E or zinc exacerbated the DNA single strand break effects at the<br />

highest concentration. Co-exposure to calcium exacerbated the single<br />

strand break effect at all concentrations.<br />

Singh et al.<br />

(1999)<br />

Xie et al.<br />

(2005)<br />

Woźniak and<br />

Blasiak (2003)

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