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Bioavailability and genotoxicity of soluble and particulate nickel compounds in cultured human lung cells

✍ Scribed by T. Schwerdtle; A. Hartwig


Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
163 KB
Volume
37
Category
Article
ISSN
0933-5137

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✦ Synopsis


Abstract

Nickel compounds are well known human and animal carcinogens, but the carcinogenic potential depends largely on the actual species. Within the present study, water soluble nickel chloride and poorly water soluble nickel oxide were compared with respect to uptake, intracellular distribution and genotoxicity as determined by the induction of DNA strand breaks and DNA base modifications recognized by the bacterial formamidopyrimidine DNA glycosylase (Fpg). The results show that both compounds were taken up by A549 cells. Furthermore, both compounds increase the nickel content in the nucleus and the cytoplasm yielding concentration ratios nucleus/cytoplasm of up to 0.18 and >0.5 for NiCl~2~ and black NiO, respectively. Also, the induction of DNA lesions was evident for water soluble and particulate nickel(II), even though pronounced effects were restricted to cytotoxic concentrations. Thus, it is proposed that nickel ions appear to be the ultimate species exerting both direct and indirect genotoxicity. The higher carcinogenic potential of particulate nickel(II) may thus be due to much longer retention times in vivo, not to different mechanisms of action on the cellular level.


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