Erythrocytes and "vinca rosea" alkaloids. An in vitro study

The reported stereoscan images have proved that overtherapeutic amounts of vincristine induce in normal red cells the same effects as vinblastine, i.e. the onset of spherocytosis (in about 30% of the cells) and spherostomatocytosis (in the remainder) associated with distinct smaller vacuoles surrounding the larger cavity. The lowest deformation-inducing doses have been found to be twice as high for vincristine as for vinblastine (0.6mM); this is probably due to the greater interaction of the latter drug (because of its methyl group) with the bilayer phospholipids. Unlike previous reports, the present findings have revealed that the onset of red cell deformation is energy independent, since the same aspects have been recorded in both young and old erythrocytes. Therefore, such deformations must be considered the morphological consequence of a drug-induced mechanical derangement of the membrane subunits. In drug-incubated normal erythrocytes it was found that (a) neither drug exerts any influence on the intraglobular energy production and/or utilization, (b) osmotic fragility is enhanced, and (c) potassium leak is increased. These findings may be considered convincingly consistent with the assumption of a drug-induced mechanical derangement of the bilayer components.