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Comparison of the metabolic activation of environmental carcinogens in mouse embryonic stem cells and mouse embryonic fibroblasts

We compared mouse embryonic stem (ES) cells and fibroblasts (MEFs) for their ability to metabolically activate the environmental carcinogens benzo[a]pyrene (BaP), 3-nitrobenzanthrone (3-NBA) and aristolochic acid I (AAI), measuring DNA adduct formation by (32)P-postlabelling and expression of xenobiotic-metabolism genes by quantitative real-time PCR. At 2 μM, BaP induced Cyp1a1 expression in MEFs

Targeted uptake of folic acid-functionalized iron oxide nanoparticles by ovarian cancer cells in the presence but not in the absence of serum

Targeted delivery of nanoparticles to cells or tissues of interest is arguably the "holy grail" of nanomedicine. Using primary human macrophages and ovarian cancer cells, we evaluated the biocompatibility and specific targeting of folic acid (FA)-conjugated iron oxide nanoparticles with organic [poly(ethylene glycol), PEG] or inorganic (SiO2) intermediate surface coatings. Reduction of folate rece

Pulmonary Inflammation Impacts on CYP1A1-Mediated Respiratory Tract DNA Damage Induced by the Carcinogenic Air Pollutant Benzo[a]pyrene

Pulmonary inflammation can contribute to the development of lung cancer in humans. We investigated whether pulmonary inflammation alters the genotoxicity of polycyclic aromatic hydrocarbons (PAHs) in the lungs of mice and what mechanisms are involved. To model nonallergic acute inflammation, mice were exposed intranasally to lipopolysaccharide (LPS; 20 µg/mouse) and then instilled intratracheally

Determination of genomic 5-hydroxymethyl-2'-deoxycytidine in human DNA by capillary electrophoresis with laser induced fluorescence

Recent studies reported the presence of 5-hydroxymethylcytosine (5 hmC) as an additional modification in mammalian genomic DNA. To date, 5 hmC has been detected only in mouse DNA isolated from embryonic stem cells, some adult tissues and in DNA from human bone marrow. Understanding its biological function will require the development of sensitive analytical methods that allow the detection and qua

Genomic N(6)-methyladenine determination by MEKC with LIF

2'-Deoxy-N(6)-methyladenosine (N(6)mdA) is frequently found in prokaryotic and unicellular eukaryotic genomes. Although methylated bases represent only a minor fraction of the genome, they, however, exhibit strong biological effects. Here, we report a fast and sensitive method for the quantification of global adenine methylation in DNA. The method is based on a recently developed procedure consist

CHRNA5 as negative regulator of nicotine signaling in normal and cancer bronchial cells : effects on motility, migration and p63 expression

Genome-wide association studies have linked lung cancer risk with a region of chromosome 15q25.1 containing CHRNA3, CHRNA5 and CHRNB4 encoding α3, α5 and β4 subunits of nicotinic acetylcholine receptors (nAChR), respectively. One of the strongest associations was observed for a non-silent single-nucleotide polymorphism at codon 398 in CHRNA5. Here, we have used pharmacological (antagonists) or gen

The carcinogenic air pollutant 3-nitrobenzanthrone induces GC to TA transversion mutations in human p53 sequences

3-Nitrobenzanthrone (3-NBA) is a potent mutagen and a suspected human carcinogen present in particulate matter of diesel exhaust and ambient air pollution. Employing an assay with human p53 knock-in (Hupki) murine embryonic fibroblasts (HUFs), we examined p53 mutations induced by 3-NBA and its active metabolite, N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA). Twenty-nine immortalized cultures (cell li

Aberrant DNA methylation links cancer susceptibility locus 15q25.1 to apoptotic regulation and lung cancer

Nicotinic acetylcholine receptor (nAChR) genes form a highly conserved gene cluster at the lung cancer susceptibility locus 15q25.1. In this study, we show that the CHRNalpha3 gene encoding the nAChRalpha3 subunit is a frequent target of aberrant DNA hypermethylation and silencing in lung cancer, whereas the adjacent CHRNbeta4 and CHRNalpha5 genes exhibit moderate and no methylation, respectively.

Use of participatory scenario modeling as platforms in stakeholder dialogues

Water related problems are characterized by complexities, uncertainties, and conflicting interests and there is no single “optimal” way to approach these “wicked” problems. Model-assisted participatory processes have been suggested as one way to meet these challenges. However, the use of models as ascenario tools for local planning of mitigation and adaptation strategies addressing environmental c

Toleransens gränser : Religionspolitiska dilemman i det tidiga 1700-talets Sverige och Europa

Var går gränsen för vilka avvikelser från samhällets grundvalar som kan tolereras? När så kallade pietister framträdde i Sverige vid 1700-talets början uppstod en ny problematik kring toleransens gränser i Sveriges historia. Till skillnad från i övriga Europa hade dessförinnan religiösa avvikare inte funnits i någon större omfattning. Pietisterna uppfattades som ett hot mot den gemensamma religion

The balance between under- and over-immunosuppression after heart transplantation with emphasis on acute cellular rejection and chronic kidney disease. Experiences from Skåne University Hospital in Lund 1988-2010

Background and aims:Heart transplantation (HT) constitutes the ultimate treatment choice for end-stage heart failure. Following HT, patients require life-long immunosuppressive treatment to prevent allograft rejection. Although survival has steadily increased over the last few decades, issues related to under- and over-immunosuppression remain common and continue to represent one of the most impor

Responding to Syncretism

Syncretism seems to disturb, and make uncertain what is taken for granted. Whether this is out of ‘logic’ or out of ‘jealousy’ is important in my reading. In this paper I suggest that logic is unhelpful in analyses of syncretism. Many religiously grounded refutations and condemnations of syncretism are based on jealousy, I suggest. I also suggest that jealousy as ground for judging syncretism, syn

Influence of spatial and temporal distribution of Turbulent Kinetic Energy on heat transfer coefficient in a light duty CI engine operating with Partially Premixed Combustion

Emission regulations together with the need of more fuel-efficient engines have driven the development of promising combustion concepts in compression ignition (CI) engines. Most of these combustion concepts, lead towards a lean and low temperature combustion potentially suitable to achieve lower emission and fuel consumption levels compared to conventional diesel combustion. In this framework, Pa

Motivating the contributions : An Open Innovation perspective on what to share as Open Source Software

Open Source Software (OSS) ecosystems have reshaped the ways how software-intensive firms develop products and deliver value to customers. However, firms still need support for strategic product planning in terms of what to develop internally and what to share as OSS. Existing models accurately capture commoditization in software business, but lack operational support to decide what contribution s

In vitro tumorigenic assay : colony forming assay for cancer stem cells

Colony forming or clonogenic assay is an in vitro quantitative technique to examine the capability of a single cell to grow into a large colony through clonal expansion. Clonogenic activity is a sensitive indicator of undifferentiated cancer stem cells. Here, we described the colony forming ability of the isolated breast cancer stem cells from the total population of cancer cells using double-laye