The tumour suppressor gene TP53 is mutated in more than 50 % of human tumours, making it one of the most important cancer genes. We have investigated the role of TP53 in cytochrome P450 (CYP)-mediated metabolic activation of three polycyclic aromatic hydrocarbons (PAHs) in a panel of isogenic colorectal HCT116 cells with differing TP53 status. Cells that were TP53(+/+), TP53(+/-), TP53(-/-), TP53(

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 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 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

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

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

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

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

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.

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

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

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

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

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

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