Halo analogs of lipids and carbohydrates: effects on Ehrlich and L1210 ascites tumors

P. Simon, P. Babiarz, L. Rittmann, T. P. Fondy

Research output: Contribution to journalArticle

Abstract

Differences in composition and synthetic pathways of lipids and carbohydrates between normal and neoplastic cells may provide chemotherapeutic approaches by means of lipid and carbohydrate analogs. The authors have synthesized 1 fluoro and 1 chloro analogs of glycerol (FG, ClG), dihydroxyacetone (FHA, CHA), cholesterol (F chol) and N acetylhexosamines, and several of their derivatives and examined the effects on in vivo development of Ehrlich ascites (EA) and L1210, as well as cytoxicity and alteration of tumorogenicity in culture. LC50's for CHA 3 benzoate and 3 phosphate were between 10-5 and 10-6M in non dividing L1210 and dividing Ehrlich cells in culture. EA tumor volume in vivo was markedly reduced or completely eradicated with these analogs as well as with the p nitro and 3,5 dinitrobenzoates, and survival was greatly extended. None of the lipid analogs was significantly active against L1210 in vivo, but pre treatment of non dividing L1210 cells in culture at the LC50 concentrations produced cells that were non tumorogenic at a challenge dose of 5x105 viable cells. Mice so treated are protected against subsequent challenge of 100 untreated L1210 cells. The corresponding glycerol analogs and the analogs of FHA were much less active than the CHA analogs. F chol produced a significant reduction in EA tumor volume on day 8, but no increased survival. Among the carbohydrate analogs N ClAc Gln showed moderate activity in vitro and in vivo.

Original languageEnglish (US)
Number of pages1
JournalProceedings of the American Association for Cancer Research
Volumevol. 17
StatePublished - Jan 1 1976

ASJC Scopus subject areas

  • Medicine(all)

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