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Protection of L5178Y Lymphoblasts by Choline and Ethanolamine against Cytocidal Effect of Nitrogen Mustard in Vitro

Gerald J. Goldenberg and B. K. Sinha
Gerald J. Goldenberg
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B. K. Sinha
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DOI:  Published June 1973
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Summary

Structural analogs of nitrogen mustard including choline and ethanolamine, previously shown to act as competitive inhibitors of nitrogen mustard (HN2) transport, have been examined for their ability to protect L5178Y lymphoblasts against the cytocidal action of HN2 in vitro. The Do (the dose of drug reducing survival to 37% of the initial cell population) for cells treated with HN2 was increased 6.5-fold in the presence of 1 mm choline and 12.7-fold in the presence of 1 mm ethanolamine, and each of these observations was highly significant (p < 0.001). Protection against HN2 was also observed with hydrolyzed HN2 and the hydrolyzed monofunctional compound, hydrolyzed dimethyl 2-chloroethylamine. The time interval between HN2 treatment and addition of protective agent was critical in that one-half the protective effect was lost if the agent was added 30 min after the drug and little protection remained at 2 hr. Exposure of cells to choline prior to HN2 treatment was no more effective than administration of choline simultaneously with drug therapy. No protection was noted in cells preloaded with choline for 20 hr and then washed immediately before HN2 treatment. These findings suggested that the mechanism of protection probably depends upon direct competition between protective agent and drug for transport into the cell. Attempts to protect mice against lethal doses of HN2 and rats from the myelosuppressive effects of drug were unsuccessful.

Footnotes

  • ↵1 This work was supported by a grant from the National Cancer Institute of Canada.

  • Received December 19, 1972.
  • Accepted March 14, 1973.
  • ©1973 American Association for Cancer Research.
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June 1973
Volume 33, Issue 6
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Protection of L5178Y Lymphoblasts by Choline and Ethanolamine against Cytocidal Effect of Nitrogen Mustard in Vitro
Gerald J. Goldenberg and B. K. Sinha
Cancer Res June 1 1973 (33) (6) 1253-1257;

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Protection of L5178Y Lymphoblasts by Choline and Ethanolamine against Cytocidal Effect of Nitrogen Mustard in Vitro
Gerald J. Goldenberg and B. K. Sinha
Cancer Res June 1 1973 (33) (6) 1253-1257;
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Cancer Research Online ISSN: 1538-7445
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