Narayan C. Rath
Keynote: J Clinic Toxicol
D ithiocarbamate (DTC) fungicides are widely used in crop protection, seed treatments, fumigants, and other household applications such as biocides, and pest repellants. Embryonic exposure to several alkyl-DTC such as thiram and disulfiram produces skeletal abnormalities. In post hatch poultry thiram and similar genre of chemicals, induce cartilage defect in growing long bones impairing endochondral bone formation. Broiler chickens fed thiram at the concentration of 50-100 mg/kg for a day or 2 succumb to the growth plate defect named tibialdyschondroplasia(TD). We studied the effects of thiram using chicken growth plates and isolated chondrocytes using metabolic, gene expression, and proteomic parameters Thiram showed toxicity to endothelial cells and transition zone chondrocytes; depleted glutathione, suppressed expression of several candidate genes involved in growth plate development, angiogenesis, and induced apoptosis. It did not interfere with chondrocyte proliferation in growth platebut impeded their hypertrophic transition, a step imperative for endochondral bone development. Proteomic studies with affected growth plate derived from chickens during early stages of disease showed changes in several proteins important in energy metabolism and signal transduction pathways. Similar studies using sublethal concentrations of thiram on chondrocytes in culture showed evidences of cellular stress that could be consequential to their apoptosis. However, the differential susceptibility of hypertrophic zone chondrocytes as compared with other developmental stages suggest that changes in membrane fluidity during hypertrophic transition possibly facilitates the incorporation of these chemicals producing their toxicological effects. The dithiocarbamate induced arrest of endochondral bone provides a good model to study skeletal toxicomics.
Narayan Rath has over 40 years of research experience. After receiving Ph.D from University of Delhi, India, he did postdoctoral work at CNRS, France, and at the National Institutes of Health, Bethesda. He has published over 100 peer reviewed papers
