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The toxic effect of androgenic and antiandrogenic substances in breast and prostate cell lines

Background

We have participated in an EU-funded project COMPRENDO, Comparative Research on Endocrine Disrupters: Phylogenetic Approach and Common Principles Focusing on Androgenic/Antiandrogenic Compounds) aimed at increasing our understanding and knowledge of endocrine disrupting chemicals (EDCs). They are natural or synthetic chemicals that mimic, enhance, or inhibit endogenous hormones. There is strong evidence obtained from laboratory studies showing the potential of several environmental chemicals to cause endocrine disruption in man and other animals at realistic exposure levels. Impaired reproduction and development causally linked to endocrine disrupting chemicals are well documented in a number of species and have resulted in local or regional population changes. In man, the decreased semen quality and increased incidence in testicular cancer world-wide has been attributed to these chemicals. Possible targets for them have been identified in the ovary. Their modes of action have also been partly identified. They interfere with apoptosis, alter cell signaling pathways, and affect estrogen metabolism. Most studies concerning endocrine disrupting chemicals have evolved around estrogenic and antiestrogenic compounds but lately, the possible endocrine interfering effects of androgenic and antiandrogenic compunds have come into focus.

Experimental system and end points

Within COMPRENDO, we have focused our work on determining dose-response effects in relation to induction of apoptosis and inhibition of cell proliferation in cell lines derived from normal and cancerous tissue from breast and prostate. A variety of different compounds with a known or suspected androgenic or antiandrogenic activity have been tested. The experimental data are presently being compiled for publication. The funding for COMPRENDO ended 2006.

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