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Protection of Ehrlich Ascites Tumor Cells against the Antiproliferative Effect of Mechlorethamine (Nitrogen Mustard) by 5-N,N-Dimethylamiloride¹

Institut für Medizinische Chemie und Biochemie, Universität Innsbruck, A-6020 Innsbruck, Austria

5-N,N-Dimethylamiloride protects Ehrlich ascites tumor cells against the antiproliferative effect of nitrogen mustard. The drug reduces the frequency of DNA interstrand cross-links introduced by nitrogen mustard. Cells with a defective choline carrier are not protected against nitrogen mustard by dimethylamiloride. As nitrogen mustard is taken up by the choline carrier, it is concluded that the recently reported inhibition of the choline transport system by amiloride and its dimethyl derivatives (W. Doppler et al., Biochem. Pharmacol, 36: 1645–1649, 1987) is responsible for the protection against the alkylating agent.

¹ These studies were supported in part by the Austrian Science Fund (Fonds zur Förderung der wissenschaftl. Forschung) Project 4690 and by the Federal Ministry for Research and Technology (Bundesministerium für Forschung und Technologie) of the Federal Republic of Germany, Study Group, "Development and Testing of New Antitumor Agents."

² To whom requests for reprints should be addressed.

Received 8/24/87. Revised 12/31/87. Accepted 1/28/88.