Obiettivo The main goal of this project is to decide whether modifications of cell signal-transduction and genomic alterations leading to programmed cell death (apoptosis) are responsible for the neurotoxic effects of a heterogeneous group of environmental toxicants. The occurrence of signalling alterations and apoptosis in cultures of neural, lymphoid cells and in tissues from exposed animals will then be used as potential end-points to evaluate neurotoxic effects, in vitro.The in vitro assessment of biological risks connected with exposure to potentially neurotoxic substances is complicated by the scarce development of sensitive and appropriate model systems and by the lack of sensitive end-points. However, a better understanding of the molecular mechanisms involved in low-level toxicity has provided new information on the cellular targets potentially affected at environmental exposure levels. Sensitive targets may include elements of the signal transduction pathways, including receptors and post-receptor messenger systems, the cytoskeleton, genes involved in growth regulation, differentiation and those responsible for the activation of a self-deletion program known as apoptosis or programmed cell death.We plan to study whether chemical agents and environmental pollutants can cause modifications of cell signalling and genomic alterations that ensue in neural cell apoptosis at concentrations comparable with in vivo exposure. To identify potential peripheral markers usable for risk assessment in exposed human populations, we will also test the effects of the selected group of compounds in lymphoid cells. We therefore propose a molecular approach to the study of potential cytotoxicity markers in human and animal cell lines, in primary neural cell cultures and in lymphoid cells. The use of these models will allow the identification of early cytotoxic markers, reflecting the in vivo features or a chronic exposure to toxicants. The use of such model systems could then be proposed not only for the study of cytotoxic processes but also for screening tests, following an adequate validation. Thus, we also plan to examine whether the findings obtained in vitro reflect disturbances in development and differentiation of the peripheral and central nervous system in exposed animals. The agents selected for these studies will be within the environmental exposure range. This can ultimately lead to the development of criteria that can be used to predict neurotoxic damage of chemical agents in vivo. Campo scientifico natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencescell biologycell signaling Programma(i) FP3-ENV 1C - Specific research and technological development programme (EEC) in the field of the environment, 1990-1994 Argomento(i) 040203 - Environment and human health Invito a presentare proposte Data not available Meccanismo di finanziamento CSC - Cost-sharing contracts Coordinatore KAROLINSKA INSTITUTE Contributo UE Nessun dato Indirizzo Nobels Vaeg, 13 171 77 STOCKHOLM Svezia Mostra sulla mappa Costo totale Nessun dato Partecipanti (2) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto UNIVERSITÀ DEGLI STUDI DELLA TUSCIA Italia Contributo UE Nessun dato Indirizzo Via S. Camillo de Lellis 01100 VITERBO Mostra sulla mappa Costo totale Nessun dato University of Milano Italia Contributo UE Nessun dato Indirizzo Via Balzaretti, 9 20133 Milano Mostra sulla mappa Costo totale Nessun dato