Polyanion induced nuclear swelling and microsphere formation

Natural and synthetic polyanions are known to have a broad spectrum of physiologic and pharmacologic properties. Some polyanions can activate in vitro nucleic acid biosynthesis in isolated nuclei, and induce varying degrees of nuclear swelling and chromatin decondensation. This in vitro phenomenon has an in vivo analog in gene activation. Pyran, a copolymer of divinyl ether and maleic anhydride, is a particularly interesting polyanion because of its antitumor, antiviral, and immunostimulating activities. Although the mechanism of its activities is unknown, its polyanionic character suggests that it may be considered as a model “gene regulator.” The present investigation focused upon the interaction of Pyran with nuclei isolated from normal mouse spleens. Small angle light scattering was used to monitor nuclear swelling, and the conditions required to demonstrate swelling were established. It was shown that Pyran-induced nuclear swelling results from the ability of this polyanion to form a complex with Mg 2+ . It was also shown by nephelometric titration methods and small angle light scattering that the interaction of Pyran and Mg 2+ resulted in the precipitation of “microspheres.” These results have led to a working hypothesis relating to the possible molecular mechanism of the pharmacologic action of Pyran copolymer.