Browsing by Author "Mayer, C."

Purpose: To test a stimulatory effect of the radioprotector Bowman Birk protease inhibitor (BBI) upon DNA repair processes. Materials and methods: An effect of BBI upon DNA repair was investigated by quantification of radiation-induced dicentric chromosomes. Sensitivity to ionizing radiation was determined by clonogenic survival assay. Quantification of activity of the DNA-dependent kinase was performed by immunoprecipitation and phosphorylation of a TP53-derived peptide. Results: The formation of radiation-induced dicentric chromosomes was reduced significantly after pretreatment of cells with BBI. By using a cell line with an inducible expression of a mutated TP53, it was shown that the BBI-mediated reduction of dicentric chromosome formation depended on the presence of wild-type TP53. To get further insights into the molecular mode of action of BBI, activity of the DNA-dependent protein kinase (DNA-PK) was quantified. BBI treatment resulted in a stimulation of basal (DNA-PK) activity. In SCID mouse fibroblasts deficient in DNA-PK activity, BBI failed to reduce the amount of radiation-induced dicentric chromosomes and the radioprotective effect was absent. Likewise, cells expressing mt.TP53 did not show radioprotection by BBI. Conclusions : It was observed that BBI exerts its radioprotective effect by a reduction of incorrect DNA repair, resulting in a reduced amount of dicentric chromosomes. This effect on the fidelity of DNA repair is TP53 dependent and correlated with induction of DNA-PK activity.

Angiotensin II (Ang II) as a vasoactive hormone may be involved in progressive renal interstitial fibrosis. We investigated the influence of Ang II on cell proliferation and synthesis of extracellular matrix (collagen I, III and fibronectin) in human renal fibroblasts derived from normal (TK 173 cell line) and fibrotic (TK 188 cell line) kidneys which possess both Ang Il type I and type 2 (AT1 and AT2) receptors. Incubation of the cells with Ang II increased the cell proliferation and the synthesis of extracellular matrix significantly in both cell lines. However, proliferation and extracellular matrix synthesis showed a greater increase in the cells derived from the fibrotic kidney. The Ang II mediated effect on cell proliferation and extracellular matrix synthesis was diminished in the presence of the AT1 receptor blocker losartan in both cell lines. No inhibition was observed using the AT2 receptor blocker PD123319. Ang II induced cell proliferation could be completely inhibited by incubation with human TGF-betal antibody. Incubation with Ang II did not affect TGF beta 1 production but in untreated cells TGF-beta 1 content was higher in the cells derived from the fibrotic kidney. This might be the reason for the more sensitive reaction on exposure to Ang II.

Since several years the implementation of an assessment licensing procedure for housing systems is discussed in Germany. In this Paper the existing legal regulations are analyzed regarding the practicability of closed integral 13a I, II of the German Animal Welfare. In addition, it is discussed if it is necessary to implement a testing procedure at the present situation. Furthermore the most important needs for the implementation of such a procedure are examined and the possible consequences are discussed.