Human lung cell growth is not stimulated by lead ions after lead chromate-induced genotoxicity.
Chromate compounds are known human lung carcinogens. Water solubility is an important factor in the carcinogenicity of these compounds with the most potent carcinogenic compounds being water-insoluble or 'particulate'. Previously we have shown that particulate chromates dissolve extracellularly releasing chromium (Cr) and lead (Pb) ions and only the Cr ions induce genotoxicity. Pb ions have been considered to have epigenetic effects and it is thought that these may enhance the carcinogenic activity of lead chromate, perhaps by stimulating Cr-damaged cells to divide. However, this possibility has not been directly tested. Accordingly, we investigated the ability of Pb ions to stimulate human lung cells and possibly force lead chromate-damaged cells to grow. We found that at concentrations of lead chromate that induced damage, human lung cells exhibited cell cycle arrest and growth inhibition that were very similar to those observed for sodium chromate. Moreover, we found that soluble Pb ions were not growth stimulatory to human lung cells and in fact induced progressive mitotic arrest. These data indicate that lead chromate-generated Cr ions cause growth inhibition and cell cycle arrest and that Pb does not induce epigenetic effects that stimulate chromate-damaged cells to grow.
Wise
Sandra S
SS
Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104-9300, USA.
Holmes
Amie L
AL
Moreland
Jonathan A
JA
Xie
Hong
H
Sandwick
Sarah J
SJ
Stackpole
Megan M
MM
Fomchenko
Elena
E
Teufack
Sonia
S
May
Alfred J
AJ
Katsfis
Spiros P
SP
Wise
John Pierce
JP
D002413:Cations, Divalent; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002840:Chromates / Q000633:toxicity; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D005971:Glutamates / Q000494:pharmacology; D006801:Humans; D007854:Lead / Q000494:pharmacology; D008168:Lung; D009153:Mutagens / Q000633:toxicity*; D017670:Sodium Compounds; D013997:Time Factors
D002413:Cations, Divalent; D002840:Chromates; D005971:Glutamates; D009153:Mutagens; D017670:Sodium Compounds; D007854:Lead; C028982:sodium chromate(VI); C031895:lead chromate