Document Type

Dissertation

Publication Date

Spring 5-5-1965

Abstract

Human neoplastic cells resistant to the antileukemic agent 6-mercaptopurine (6-MP) were examined in tissue culture to study the glycolytic activity of resistant cells. The media, with and without 6-MP, of three neoplastic cell lines, HeLa, HEp-2, and J-lll was compared for glucose and lactate concentrations before and after incubation. It was found that in the media of HeLa and HEp-2 cells exposed to 6-MP glucose disappearance and lactate formation was enhanced. It was also found, however, that glucose and lactate concentrations of the media of 6-MP resistant HeLa and HEp-2 cells were not altered by the activity of 6-MP. On the other hand, in the media of J-lll cells both sensitive and resistant to 6-MP glucose and lactate concentrations were not changed by the activity of 6-MP. The results indicate that with the development of resistance to 6-MP, HeLa and HEp-2 cells no longer are stimulated by 6-MP to use extracellular glucose at an increased rate. It is also known that when HeLa and HEp-2 cells develop resistance to 6-MP there is an associated inability of both cell types to form the 6-MP ribonucleotide. The interrelationships of these two findings is not known; although it is suggested that both cell types develop resistance by a common pathway. However, because glycolytic activity in J-lll cells is not stimulated by 6-MP it is suggested that resistance may develop by still another mechanism.

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