THE ORGANOCHLORINE HERBICIDE CHLORIDAZON INTERACTS WITH CELL-MEMBRANES

Chloridazon is a widely used organochlorine herbicide. In order to eva luate its perturbing effect on cell membranes it was made to interact with human erythrocytes, frog adrenergic neuroepithelial synapse and m olecular models. These consisted in multilayers of dimyristoylphosphat idylethanolamine (DMPE) and of dimyristoylphosphatidyltidylcholine (DM PC), representative of phospholipid classes located in the inner and o uter monolayers of the erythrocyte membrane, respectively. X-ray diffr action showed that chloridazon interacted preferentially with DMPC mul tilayers. Scanning electron microscopy revealed that 0.1 mM chloridazo n induced erythrocyte crenation. According to the bilayer couple hypot hesis, this is due to the preferential insertion of chloridazon in the phosphatidylcholine-rich external moiety of the red cell membrane. El ectrophysiological measurements showed that nerve stimulation was foll owed immediately by a transient increase in short-circuit current (SCC ) and in the potential difference (PD) of the neuroepithelial synapse. Increasing concentrations of chloridazon caused a dose-dependent and reversible decrease of the responses of both parameters to 76% of thei r control values. The pesticide induced a similar (28%) significant ti me-dependent decrease in the basal values of the SCC and of PD. These results are in accordance with a perturbing effect of chloridazon on t he phospholipid moiety of the nerve fibre membrane leading to interfer ence with total ion transport across the nerve skin junction. (C) 1998 Elsevier Science Inc. All rights reserved.