Immunomodulation by a semiquinone free radical: evidence implicating T lymphocyte involvement

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Title: Immunomodulation by a semiquinone free radical: evidence implicating T lymphocyte involvement
Author: Morgan, Clinton David
Abstract: Numerous natural and synthetic quinone compounds possess significant anticancer properties . Various mechanisms have been proposed to account for these properties , including tumor cell DNA scission and degradation , intracellular "redox cycling" to cogenerate semiquinone radicals and reactive oxygen intermediates , and the interaction of semiquinone radicals with tumor cell surface membrane flavoenzymes . No evidence has been presented , however , to adequately explain the preferential attack on tumor cells by semiquinone radicals , as opposed to normal cells . To address this question , an immunologic interaction was examined . A therapy of Ehriich ascites tumor , consisting of a mixture of 750 mM L -ascorbate and 3 mM 2 ,6 - dimethoxy -p -benzoquinone as described by R . Pethig and associates , was used for in vitro and in vivo evaluation . This therapy was employed to generate micromolar quantities of a long -lived semiquinone radical and was found to exert a transient in vivo cytostatic influence against the tumor cells . This semiquinone radical was further found to be ineffective in immunodeficient BALB /c mice at mediating tumor regression . The radical was ineffective in sublethally irradiated mice , in cyclosporin A -treated mice , and in athymic mice . The antitumor efficacy of the radical was maintained , however , in selenium -deficient mice . These results suggested that the antitumor effect of the radical was immunologically mediated , with the T lymphocyte as the primary cellular candidate . BALB /c mice were depleted of functional T lymphocytes by xenogeneic monoclonal antibody pretreatment , challenged with the tumor , and treated with the semiquinone radicalgenerating therapy . Mice depleted of CD4+ T lymphocytes responded with enhanced tumor progression and significant decreases in life expectancies over controls . Less severe responses were observed in mice devoid of CD8+ T lymphocytes . Mice depleted of both T subpopulations responded with very rapid tumor growth and mortalities . When tumor challenge occurred after the treatment , mice enriched for CD4+ T lymphocytes delayed tumor progression and demonstrated significant increases in life expectancies over controls . The immunologic component of the semiquinone radical interaction hypothesis was clearly shown to be the T helper /inducer lymphocyte , indicating a synergistic phenomenon of radical -induced cytostasis and immunomodulation of T lymphocyte helper activity to promote the inhibition of tumor progression .
URI: http : / /hdl .handle .net /2346 /11199
Date: 1992-12


Morgan, Clinton David Immunomodulation by a semiquinone free radical: evidence implicating T lymphocyte involvement. Doctoral dissertation, Texas Tech University. Available electronically from http : / /hdl .handle .net /2346 /11199 .

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