SYNERGISM OF DIMETHOXYBENZOSEMIQUINONE FREE-RADICALS AND CD4-LYMPHOCYTES TO SUPPRESS EHRLICH ASCITES TUMOR( T)

Numerous natural and synthetic quinone compounds possess significant a ntitumor properties, Various mechanisms have been proposed to account for these properties, including scission and degradation of tumor cell DNA, intracellular ''redox cycling'' to cogenerate semiquinone free r adicals and reactive oxygen intermediates, and the interaction of semi quinone radicals with tumor cell surface flavoenzymes, However, no evi dence has been presented to explain adequately the preferential attack on tumor cells by semiquinone radicals, as opposed to normal cells, T o address this question, a synergistic interaction was examined, A the rapy consisting of a mixture of L-ascorbate and 2, 6-dimethoxy-p-benzo quinone, was used for in vivo evaluation. BALB/c mice were depleted of functional T-lymphocytes by xenogeneic monoclonal antibody pretreatme nt, challenged with Ehrlich ascites tumor, and administered the semiqu inone radical-generating therapy. Mice depleted of CD4+ T-lymphocytes responded with rapidly fatal tumor progression, with significantly dec reased mean survival times over controls, whereas less severe response s were observed in mice devoid of CD8+ T-lymphocytes. Mice depleted of both T-lymphocyte subpopulations responded with uninhibited tumor gro wth and rapid mortalities, When tumor challenge occurred after therapy , tumor growth was significantly delayed in mice enriched for CD4+ T-l ymphocytes, with demonstrable increases in mean survival time over con trols. This reagent combination had no significant effect on T-lymphoc yte profiles in secondary lymphoid organs. These data suggest a synerg istic phenomenon of semiquinone radical-induced cytostasis coupled wit h T-lymphocyte helper activity for optimal tumor suppression.