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87469 
Journal Article 
Effect of nickel and iron co-exposure on human lung cells 
Salnikow, K; Li, X; Lippmann, M 
2004 
Yes 
Toxicology and Applied Pharmacology
ISSN: 0041-008X
EISSN: 1096-0333 
196 
2 
258-265 
8 
English 
15081272 
WOS:000220908900008 
Exposure to ambient air particulate matter (PM) is associated with increased mortality and morbidity in susceptible populations. The epidemiological data also suggest a relationship between PM air pollution and impairment of cardiopulmonary function. The mechanisms that may be responsible for these effects are not fully understood and are likely related to perturbations of cellular and molecular functions. One type of PM, residual oil fly ash (ROFA), is of particular interest. ROFA does not contain much organic material, but does contain relatively high quantities of transition metals, predominantly nickel, vanadium, and iron, as well as black carbon and sulfates. In this study, we investigated the effect of two metals (iron and nickel) on the induction of "hypoxia-like" stress and the production of interleukins (ILs) in minimally transformed human airway epithelial cells (1HAEo-). We found that exposure to soluble nickel sulfate results in the induction of hypoxia-inducible genes and IL-8 production by the 1HAEo- cells. The simultaneous addition of iron in either ferric or ferrous form and nickel completely inhibited IL-8 production and had no effect on "hypoxia-like" stress caused by nickel, suggesting the existence of two different pathways for the induction "hypoxia-like" stress and IL-8 production. The effect of nickel was not related to the blocking of iron entry into cells since the level of intracellular iron was not affected by co-exposure with nickel. The obtained data indicate that nickel can induce different signaling pathways with or without interference with iron metabolism. Our observations suggest that in some cases the excess of iron in PM can cancel the effects of nickel. 
ROFA;nickel;iron;ferritin;hypoxia-inducible genes;IL-8;OIL FLY-ASH;HYPOXIA-INDUCIBLE FACTOR;EPITHELIAL-CELLS;TRANSITION-METALS;AIR-POLLUTION;HIF-ALPHA;RAT LUNG;EXPOSURE;OXYGEN;INJURY;PHARMACOLOGY & PHARMACY;TOXICOLOGY 
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