Probable immune system mediation of the antitumor activity of the 2,6-dimethoxybenzo-p-semiquinone radical.
We recently reported that the antitumor activity of an immobilized oxidase-peroxidase system, which can produce radical species as intermediates, is dependent on the presence of an intact and functioning immune system in the host. A number of recent investigations have indicated that the bioactive form of many quinone-type anticancer agents may be the semiquinone-type radical. To investigate if the antitumor activity of some of the quinone-type anticancer agents may also be dependent on a fully functioning immune system in the host, we used as a simple, well-defined model the 2,6-dimethoxybenzo-p-semiquinone radical. This free radical has a potent antitumor activity against Ehrlich ascites tumors in mice, as first described by Szent-Gyorgyi's group. In the present study, we investigated its antitumor activity in immunocompromised BALB/c mice. We found that the antitumor activity of the semiquinone radical is completely abolished in mice that had previously been subjected to whole body gamma irradiation, indicating a possible involvement of one or more cells of the host's defense system. The antitumor activity was not abolished in mice with dysfunctional macrophages induced by a severe selenium deficiency. However, the radical was inactive in mice whose immune system was suppressed with cyclosporin A and in nude (nu/nu) mice. These results suggest that the dimethoxybenzo-semiquinone radical, rather than acting primarily as a cytotoxic agent as previously reported, exerts its antitumor activity mainly via a more complex mechanism in which T lymphocytes appear to play a major role.
Morgan
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Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock 79430.
Combs
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SH
Everse
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D016572:Cyclosporine / Q000494:pharmacology; D007107:Immune System / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012643:Selenium / Q000172:deficiency; D013601:T-Lymphocytes / Q000502:physiology; D014916:Whole-Body Irradiation
D000970:Antineoplastic Agents; D016227:Benzoquinones; C025232:semiquinone radicals; D016572:Cyclosporine; D012643:Selenium