Management and Good Laboratory Practice at the Division Biological Evaluation of Drug effects of the Central Animal Laboratory

The department BES (Biological Evaluation of Drug Effects) carries out animal studies for RIVM laboratories, whose commitment to GLP makes it necessary for BES also to comply with GLP. Compliance is assured by means of a quality system laid down in a quality handbook quaranteeing the consistent quality of the department products. The elements of the BES quality system are documented in this report under the following headings: - quality targets and management organisation - survey of areas of competence and of stoff qualifications - equipment inventory - goods and services available - standard operating procedures. Furthermore a general servey is presented of those co-operative arrangements necessary for optimal departmental organization.RIV

Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress

OBJECTIVE: We have previously identified peroxiredoxin-3 (PRDX-3) as a cell-surface protein that is androgen regulated in the LNCaP prostate cancer (PCa) cell line. PRDX-3 is a member of the peroxiredoxin family that are responsible for neutralising reactive oxygen species. EXPERIMENTAL DESIGN: PRDX-3 expression was examined in tissue from 32 patients using immunohistochemistry. Subcellular distribution was determined using confocal microscopy. PRDX-3 expression was determined in antiandrogen-resistant cell lines by western blotting and quantitative RT–PCR. The pathways of PRDX-3 overexpression and knockdown on apoptosis and response to oxidative stress were investigated using protein arrays. RESULTS: PRDX-3 is upregulated in a number of endocrine-regulated tumours; in particular in PCa and prostatic intraepithelial neoplasia. Although the majority of PRDX-3 is localised to the mitochondria, we have confirmed that PRDX-3 at the cell membrane is androgen regulated. In antiandrogen-resistant LNCaP cell lines, PRDX-3 is upregulated at the protein but not RNA level. Resistant cells also possess an upregulation of the tricarboxylic acid (TCA) pathway and resistance to H(2)O(2)-induced apoptosis through a failure to activate pro-apoptotic pathways. Knockdown of PRDX-3 restored H(2)O(2) sensitivity. CONCLUSION: Our results suggest that PRDX-3 has an essential role in regulating oxidation-induced apoptosis in antiandrogen-resistant cells. PRDX-3 may have potential as a therapeutic target in castrate-independent PCa