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2 Journal of Applied Genetics

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Differences between rats and mice in induction of 4S beta-naphthoflavone-binding protein expression by treatment with beta-naphthoflavone

100%

Brauze D. , Januchowski R. , Szyfter K.

nr 3

371-376

Sprague-Dawley rats and several inbred strains of mice were compared with respect to the induction of 4S BNF-binding protein expression by treatment with beta-naphthoflavone (BNF), an aryl hydrocarbon receptor (AhR) ligand. Inbred strains of mice chosen for the study encompassed 3 allelic forms of AhR found in Mus musculus so far. As it was reported by us earlier, treating rats with BNF caused a significant induction of BNF-binding protein expression. By contrast, no BNF-binding protein was detected in mice treated with BNF in corn oil as a vehicle or with corn oil itself.

Role of epigenetic DNA alterations in the pathogenesis of systemic lupus erythematosus

100%

Januchowski R. , Prokop P. , Jagodzinski P. P.

Journal of Applied Genetics

2004

tom 45

nr 2

237-248

Epigenetic alternations in genomic DNA encompass cytosine methylation in cytosine and guanine (CpG) dinucleotide islands, which are usually extended in the promoter and first exon of genes. The DNA methylation is carried out by DNA methyltransferases (DNMT) and it serves as an epigenetic method of gene expression modulation. The epigenetic alternations in genomic DNA have been implicated in the development of malignant and autoimmune diseases. The epigenetic aberration in regulatory DNA sequences may also be responsible for the emergence of changes in the immune system in patients with systemic lupus erythematosus (SLE). The agents 5-azacytidine (azacitidine) and 5-aza-2?-deoxycytidine (decitabine) belong to inhibitors of methyltransferase. These compounds affect the methylation level of promoter sequences and cause phenotypic changes in peripheral blood mononuclear cells (PBMC), which are similar to those observed in PBMC of SLE patients. The lack of methylcytosine in CpG dinucleotides may be responsible for the antigenic properties of microbial DNA. The presence of low-apoptotic methylated DNA fragments has been identified in plasma of SLE patients. These DNA fragments exhibit antigenic properties and may elicit the humoral response responsible for the flare of SLE. The low methylation of CpG residues in the regulatory sequences may also contribute to the elevated expression of human endogenous retroviruses (HERVs) in PBMC of SLE patients. The HERV components exhibit a profound similarity with nuclear antigens and may be responsible for the enhancement of the production of anti-antinuclear antibodies (ANA). Recent advances in the investigation of epigenetic DNA changes have formed the basis of improved understanding of etiopathogenesis of SLE, which may thereby facilitate improvement in therapeutic principles of this disease.