Document Detail


Reductive activation of hexavalent chromium by human lung epithelial cells: generation of Cr(V) and Cr(V)-thiol species.
MedLine Citation:
PMID:  18279960     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chromium(VI) compounds (e.g. chromates) are cytotoxic, mutagenic, and potentially carcinogenic. The reduction of Cr(VI) can yield reactive intermediates such as Cr(V) and reactive oxygen species. Bronchial epithelial cells are the primary site of pulmonary exposure to inhaled Cr(VI) and are the primary cells from which Cr(VI)-associated human cancers arise. BEAS-2B cells were used here as a model of normal human bronchial epithelium for studies on the reductive activation of Cr(VI). Cells incubated with Na(2)CrO(4) exhibited two Cr(V) ESR signals, g=1.979 and 1.985, which persisted for at least 1h. The g=1.979 signal is similar to that generated in vitro by human microsomes and by proteoliposomes containing P450 reductase and cytochrome b(5). Unlike many cells in culture, these cells continued to express P450 reductase and cytochrome b(5). Studies with the non-selective thiol oxidant diamide indicated that the g=1.985 signal was thiol-dependent whereas the g=1.979 signal was not. Pretreatment with phenazine methosulfate eliminated both Cr(V) signals suggesting that Cr(V) generation is largely NAD(P)H-dependent. ESR spectra indicated that a portion of the Cr(VI) was rapidly reduced to Cr(III). Cells incubated with an insoluble chromate, ZnCrO(4), also generated both Cr(V) signals, whereas Cr(V) was not detected with insoluble PbCrO(4). In clonogenic assays, the cells were very sensitive to Na(2)CrO(4) and ZnCrO(4), but considerably less sensitive to PbCrO(4).
Authors:
Griselda R Borthiry; William E Antholine; Judith M Myers; Charles R Myers
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-01-08
Journal Detail:
Title:  Journal of inorganic biochemistry     Volume:  102     ISSN:  1873-3344     ISO Abbreviation:  J. Inorg. Biochem.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-11     Completed Date:  2008-08-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7905788     Medline TA:  J Inorg Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1449-62     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
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MeSH Terms
Descriptor/Qualifier:
Carcinogens, Environmental / metabolism*
Chromates / metabolism
Chromium / metabolism*
Cytochromes b5
Electron Spin Resonance Spectroscopy
Epithelial Cells / enzymology,  metabolism*
Hazardous Substances
Humans
Lung / cytology*
Microsomes / enzymology,  metabolism
NADPH-Ferrihemoprotein Reductase
Oxidation-Reduction
Proteolipids / metabolism
Sulfhydryl Compounds
Grant Support
ID/Acronym/Agency:
EB001980/EB/NIBIB NIH HHS; ES012707/ES/NIEHS NIH HHS; R01 ES012707-04/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Carcinogens, Environmental; 0/Chromates; 0/Hazardous Substances; 0/Proteolipids; 0/Sulfhydryl Compounds; 0/proteoliposomes; 18540-29-9/chromium hexavalent ion; 7440-47-3/Chromium; 9035-39-6/Cytochromes b5; EC 1.6.2.4/NADPH-Ferrihemoprotein Reductase
Comments/Corrections

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