MECHANISMS OF THE SYNERGISTIC EFFECT OF ORAL DIMETHYL SULFOXIDE ON ANTINEOPLASTIC THERAPY*

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Abstract
The purpose of this study was to determine whether dimethyl sulfoxide (DMSO) when administered in conjunction with antitumor drugs would potentiate their activity against a rodent tumor. Twelve compounds of diverse modes of action were examined using standard protocols of the National Cancer Institute. Median survival time and median tumor diameter were the parameters used for determining any synergistic effects of DMSO when it was ingested in the drinking water and the drug administered parenterally. The continuous ingestion of DMSO alone mixed in drinking water at concentrations between 0.25-32% was not toxic and had no effect on the tumor. Although the intraperitoneal inoculation of drugs into animals ingesting DMSO did not enhance drug effectiveness, when both DMSO and drug were added to the drinking water, it did increase antineoplastic potency. DMSO ingestion also inhibited the tumor growth rate of several parenterally administered drugs even though these same compounds failed to prolong the survival time of tumor-bearing rats. The toxicity of 12 compounds when combined with DMSO was only moderately increased in four instances. Orally ingested DMSO was found to cause a twofold increase in the concentration of labeled CPA in plasma, brain, and liver tissues. This elevation persisted for approximately two to three hours but subsequently returned to the same level as that observed in water-fed rodents. The DMSO-enhancement of tissue levels coupled with a more rapid drug rate clearance offers one explanation for the therapeutic benefit noted when oral DMSO was administered concomitantly with CPA.