Submitted to: Poultry Science Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2003
Publication Date: 7/6/2003
Citation: RATH, N.C., RICHARDS, M.P., HUFF, W.E., BALOG, J.M., HUFF, G.R. Effects of Pyrrolidine Dithiocarbamate (PDTC) on Chicken Chondrocyte in Culture.. POULTRY SCIENCE MEETING. 2003. VOL 82 (Suppl. 1), p. 30. Interpretive Summary:
Technical Abstract: Tibial dyschondroplasia (TD) is a metabolic cartilage disease of fast growing poultry for which the pathogenetic mechanisms are not understood. Certain dithiocarbamate fungicides such as thiram induce TD in chickens providing a useful experimental model to study its pathogenesis. However, unlike its monomeric component dimethyl dithiocarbamate (DMTC), thiram is water insoluble making its use tricky in cell culture, and DMTC is a poor inducer of TD. We recently found pyrrolidine dithiocarbamate (PDTC), a water-soluble dithiocarbamate, to be capable of inducing TD when fed to chickens. To understand, how PDTC may lead to the induction of TD, we studied its effects on tibial growth plate-chondrocytes in culture using selective genes that are essential for growth plate metabolism such as cartilage development, matrix modeling, and angiogenesis. Duplicate cultures were treated with 10 micro m PDTC for 0, 6, and 24 h, RNA extracted, and subjected to RT-PCR. The PCR products were separated and quantified using capillary electrophoresis and laser induced fluorescence detection. We determined the expression of different genes relative to ß-actin and compared the results at 6- and 24 h to the 0 h treatment-group. Our results show that PDTC treatment down regulated the expression of most of the genes although the magnitude of changes varied depending on gene types. Type II collagen, nitric oxide synthase, and matrix metalloproteinase-2 showed time dependent down regulation whereas both type X collagen and ovotransferrin were transiently down regulated at 6h but appeared to recover by 24 h. The TGF-ß, glyceraldehyde phosphate dehydrogenase, and vascular endothelial growth factor genes appeared to maintain a steady level after a transient down regulation at 6h. These results suggest that PDTC may cause a general metabolic slow down of chondrocytes thereby impeding their developmental maturation during a chronic exposure to this chemical.