کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2570550 1128590 2008 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro expression of hard metal dust (WC–Co) — responsive genes in human peripheral blood mononucleated cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
In vitro expression of hard metal dust (WC–Co) — responsive genes in human peripheral blood mononucleated cells
چکیده انگلیسی

Hard metals consist of tungsten carbide (WC) and metallic cobalt (Co) particles and are important industrial materials produced for their extreme hardness and high wear resistance properties. While occupational exposure to metallic Co alone is apparently not associated with an increased risk of cancer, the WC–Co particle mixture was shown to be carcinogenic in exposed workers. The in vitro mutagenic/apoptogenic potential of WC–Co in human peripheral blood mononucleated cells was previously demonstrated by us. This study aimed at obtaining a broader view of the pathways responsible for WC–Co induced carcinogenicity, and in particular genotoxicity and apoptosis. We analyzed the profile of gene expression induced in vitro by WC–Co versus control (24 h treatment) in human PBMC and monocytes using microarrays. The most significantly up-regulated pathways for WC–Co treated PBMC were apoptosis and stress/defense response; the most down-regulated was immune response. For WC–Co treated monocytes the most significantly up- and down-regulated pathways were nucleosome/chromatin assembly and immune response respectively. Quantitative RT-PCR data for a selection of the most strongly modulated genes (HMOX1, HSPA1A, HSPA1L, BNIP3, BNIP3L, ADORA2B, MT3, PLA2G7, TNFAIP6), and some additionally chosen apoptosis related genes (BCL2, BAX, FAS, FASL, TNFα), confirmed the microarray data after WC–Co exposure and demonstrated limited differences between the Co-containing compounds. Overall, this study provides the first analysis of gene expression induced by the WC–Co mixture showing a large profile of gene modulation and giving a preliminary indication for a hypoxia mimicking environment induced by WC–Co exposure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 227, Issue 2, 1 March 2008, Pages 299–312
نویسندگان
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