Protection of Ehrlich ascites tumor cells against the antiproliferative effect of mechlorethamine (nitrogen mustard) by 5-N,N-dimethylamiloride.
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.
Doppler
W
W
Institut für Medizinische Chemie und Biochemie, Universität Innsbruck, Austria.
Hofmann
J
J
Maly
K
K
Grunicke
H H
HH
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002794:Choline / Q000493:pharmacokinetics / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000378:metabolism; D008466:Mechlorethamine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; C039465:5-dimethylamiloride; D008466:Mechlorethamine; D000584:Amiloride; D002794:Choline