THE ORGANOCHLORINE PESTICIDE HEPTACHLOR DISRUPTS THE STRUCTURE OF MODEL AND CELL-MEMBRANES

Heptachlor is an organochlorine pesticide which is particularly toxic for aquatic life. A significant source of this pesticide for infants i s breast milk, where its concentration is considerably higher than in dairy milk. Given the lipophilic character of heptachlor, lipid-rich c ell membranes are a very plausible target for its interaction with liv ing organisms. In order to evaluate its toxicity towards cell membrane s, heptachlor was made to interact with human erythrocytes and molecul ar models of the red cell membrane. These consisted of multilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethan olamine (DMPE), which are types of phospholipids that are respectively located in the outer and inner monolayers of the erythrocyte membrane , and large unilamellar vesicles (LUV) of DMPC. Observations by scanni ng electron microscopy showed that 10 mM heptachlor produced Various d egrees of shape alterations to erythrocytes, which ranged from a few b lebs in some cells to a great number of protuberances in others. On th e other hand, experiments performed by X-ray diffraction on DMPC and D MPE indicated that the bilayer structure of DMPC was much more affecte d by heptachlor than that of DMPE. Measurements by fluorescence spectr oscopy on DMPC LW confirmed the X-ray diffraction results in that both the hydrocarbon chain and polar head regions of DMPC were structurall y perturbed by heptachlor, The results obtained from the model studies could explain the shape changes induced to red cells by heptachlor. A ccording to the bilayer hypothesis, they were due to the preferential interaction of heptachlor with the phosphatidylcholine-rich external m oiety of the erythrocyte membrane. It is therefore concluded that toxi c effects of this pesticide can be related to its capacity to perturb the phospholipid bilayer structure, whose integrity is essential for c ell membrane functions.