Inhibition of lymphocyte DNA-synthetic responses by spermine-derived polycations

Abstract

The polyamines putrescine, spermidine, and spermine are oxidized by the enzyme diamine oxidase to form the corresponding aldehyde derivatives. These aldehydes have been shown to undergo a variety of spontaneous reactions, some of which result in polycationic addition compounds. We have chemically synthesized some spermine-derived polycations by reaction with the dialdehyde glutaraldehyde followed by reduction of the resulting Schiff base with sodium borohydride. Their migration on ion exchange and gel filtration columns was consistent with the formation of polycations with properties similar to those reported for the spontaneous reaction products. When added to cultures of alloantigen or mitogen stimulated lymphocytes, these polycations were potent inhibitors of the incorporation of tritiated thymidine and blast cell formation. This inhibition was reversible, non-cytotoxic, and only apparent if the polycation was added early in the culture period. The concentration of polycation necessary to achieve 50% inhibition of the lymphocyte response decreased as the cationic nature relative to spermine increased.