In vitro inhibition of nitrogen mustard efficacy by postincubation of treated cells in serum protein |
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Authors: | C Ritter R J Rutman C Prood |
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Institution: | Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104. |
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Abstract: | 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. |
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