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The Effect of pH upon the Antitumor Activity and Toxicity of Nitrogen Mustard¹

Cancer Research Laboratory, University of Western Ontario, London, Ontario, Canada

Mice were given single injections of HN2 solution at pH 8 or pH 2. The alkaline preparation had an LD₅₀ of about 2 mg/kg while that for the acidic preparation was about 5 mg/kg. A similar difference in toxicity was seen when the HN2 was given as a series of small daily doses. The greater toxicity of the alkaline preparation was manifest also in the hematologic findings, and in the earlier deaths of mice given this preparation. Using animals bearing either the L-1210 ascites tumor or the Ehrlich ascite tumor, a daily dose of the alkaline solution of nitrogen mustard was found which had a better antitumor effect than did the acidic solution. This finding suggests that an acidic solution of mustard does not have a preferential effect on tumor tissue compared with other tissues, and therefore an acidic solution of mustard offers no chemotherapeutic advantage over an alkaline solution.

¹ Financial support for this study was provided by the National Cancer Institute of Canada.

Received 5/21/65. Revised 11/29/65.