Neuropathy Target Esterase in Blood Lymphocytes
Marcello Lotti · ACS symposium series · 1988
Selective toxicity is initiated by specific interactions of the toxin with primary targets. The identification of such targets and their accessibility in human fluids will allow an evaluation of dose-effect relationships at a molecular level. Inter- and intra-individual variations of dose response relationships may then be rationalized and acceptable thresholds properly set. However, the assumption is made that the ultimate toxin is equally delivered to the accessible target and to where toxicity takes place. Some organophosphorus (OP) pesticides cause a rare selective toxicity called organophosphate-induced delayed polyneuropathy (OPIDP). The initiation of this toxicity involves specific interactions of a protein in the nervous system called Neuropathy Target Esterase (NTE). This protein is present in blood lymphocytes and its measurement after exposure to certain OP pesticides has been suggested as a biomonitor for OPIDP. NTE inhibition in blood lymphocytes predicts the development of OPIDP in man. However dose-response relationships are not available for man and a threshold is not yet established. Human lymphocytic NTE shows large interindividual variation, suggesting the need for an individual baseline to evaluate occupational exposures. An attempt to monitor occupational exposures showed a substantial effect on lymphocytic NTE not followed by toxicity. A likely explanation is that the assumption on the delivery previously made was incorrect. Furthermore the turnover of NTE in the target organ might be faster than in the monitored one and thus the effect of exposure overestimated.