44 research outputs found
Compression of Interstellar Clouds in Spiral Density-Wave Shocks
Wetensch. publicati
Comparison of Gene Expression Profiles in Chromate Transformed BEAS-2B Cells
Hexavalent chromium [Cr(VI)] is a potent human carcinogen.
Occupational exposure has been associated with increased risk of respiratory
cancer. Multiple mechanisms have been shown to contribute to Cr(VI) induced
carcinogenesis, including DNA damage, genomic instability, and epigenetic
modulation, however, the molecular mechanism and downstream genes mediating
chromium's carcinogenicity remain to be elucidated.We established chromate transformed cell lines by chronic exposure of normal
human bronchial epithelial BEAS-2B cells to low doses of Cr(VI) followed by
anchorage-independent growth. These transformed cell lines not only
exhibited consistent morphological changes but also acquired altered and
distinct gene expression patterns compared with normal BEAS-2B cells and
control cell lines (untreated) that arose spontaneously in soft agar.
Interestingly, the gene expression profiles of six Cr(VI) transformed cell
lines were remarkably similar to each other yet differed significantly from
that of either control cell lines or normal BEAS-2B cells. A total of 409
differentially expressed genes were identified in Cr(VI) transformed cells
compared to control cells. Genes related to cell-to-cell junction were
upregulated in all Cr(VI) transformed cells, while genes associated with the
interaction between cells and their extracellular matrices were
down-regulated. Additionally, expression of genes involved in cell
proliferation and apoptosis were also changed.This study is the first to report gene expression profiling of Cr(VI)
transformed cells. The gene expression changes across individual chromate
exposed clones were remarkably similar to each other but differed
significantly from the gene expression found in anchorage-independent clones
that arose spontaneously. Our analysis identified many novel gene expression
changes that may contribute to chromate induced cell transformation, and
collectively this type of information will provide a better understanding of
the mechanism underlying chromate carcinogenicity
Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes
A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s11671-014-0707-0) contains supplementary material, which is available to authorized users