title: Synergism of dimethoxybenzosemiquinone free radicals and CD4+ T-lymphocytes to suppress Ehrlich ascites tumor.
abstract: Numerous natural and synthetic quinone compounds possess significant antitumor 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 radicals and reactive oxygen intermediates, and the interaction of semiquinone radicals with tumor cell surface flavoenzymes. However, no evidence has been presented to explain adequately the preferential attack on tumor cells by semiquinone radicals, as opposed to normal cells. To address this question, a synergistic interaction was examined. A therapy consisting of a mixture of L-ascorbate and 2,6-dimethoxy-p-benzoquinone, was used for in vivo evaluation. BALB/c mice were depleted of functional T-lymphocytes by xenogeneic monoclonal antibody pretreatment, challenged with Ehrlich ascites tumor, and administered the semiquinone radical-generating therapy. Mice depleted of CD4+ T-lymphocytes responded with rapidly fatal tumor progression, with significantly decreased mean survival times over controls, whereas less severe responses were observed in mice devoid of CD8+ T-lymphocytes. Mice depleted of both T-lymphocyte subpopulations responded with uninhibited tumor growth and rapid mortalities. When tumor challenge occurred after therapy, tumor growth was significantly delayed in mice enriched for CD4+ T-lymphocytes, with demonstrable increases in mean survival time over controls. This reagent combination had no significant effect on T-lymphocyte profiles in secondary lymphoid organs. These data suggest a synergistic phenomenon of semiquinone radical-induced cytostasis coupled with T-lymphocyte helper activity for optimal tumor suppression.
authors.affiliation: Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Morgan
authors.forename: S S
authors.initials: SS
authors.lastname: Lefkowitz
authors.forename: J
authors.initials: J
authors.lastname: Everse
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D016227:Benzoquinones / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002286:Carcinoma, Ehrlich Tumor / Q000628:therapy*; D002454:Cell Differentiation; D003131:Combined Modality Therapy; D005260:Female; D005609:Free Radicals; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016227:Benzoquinones; D005609:Free Radicals; C030511:2,6-dimethoxy-1,4-benzoquinone; D001205:Ascorbic Acid