In vitro inhibition of nitrogen mustard efficacy by postincubation of treated cells in serum protein.
Lettre-Ehrlich cells were loaded with sufficient HN2 to produce about a 98% cell kill. Postincubation of the HN2-loaded cells in PBS resulted in the loss of about 40% of their HN2 without changing the cytolytic effect, supporting the proposal that only bound drug was effective. Postincubation of the HN2-loaded cells in PBS which contained 2% bovine serum albumin or in cell-free mouse ascitic fluid (1.8% protein) resulted in the same relative cellular HN2 loss as well as a 79% decrease in the cell kill. The cytolytic effect of HN2 is believed to be dependent on the degree to which the drug crosslinks DNA in 2 sequential reactions. It seems likely that such crosslinking occurred in nearly all of the PBS-postincubated cells, as they were nearly all killed. By analogy, albumin postincubation apparently blocked the competition of such crosslinking.
Ritter
C
C
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Rutman
R J
RJ
Prood
C
C
D000818:Animals; D001202:Ascitic Fluid; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology; D003470:Culture Media / Q000494:pharmacology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004705:Endocytosis; D008081:Liposomes; D008466:Mechlorethamine / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D051379:Mice; D011506:Proteins / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D003470:Culture Media; D004273:DNA, Neoplasm; D008081:Liposomes; D011506:Proteins; D012710:Serum Albumin, Bovine; D008466:Mechlorethamine; D002118:Calcium