Effects of theophylline on the cell growth of normal and malignant human cells transformed in culture.

Abstract

Proliferation of normal human diploid cell strains was inhibited to a greater extent by treatment with theophylline than the proliferation of neoplastic human cell lines transformed in culture with Co-60 gamma rays (WI-38 CT-1) or SV40 (WI-38 VA-13). Theophylline was added to cultures at final concentrations of 1 to 3 mM. Morphologically, normal fibroblasts became slender and small when grown in theophylline-containing medium, while little morphological change was observed in neoplastically transformed cells. Growth inhibition of theophylline was cytostatic rather than cytotoxic. No significant difference was detected in the uptake of theophylline between the normal and the transformed cells. Incorporation of 3H-thymidine into acid-insoluble fractions of cells began to decrease in the normal cells about 4 hr after adding theophylline to the culture medium. The intracellular contents of adenosine 3',5'-cyclic monophosphate increased linearly in the normal human cells with the time of treatment with theophylline, but no increase was observed in the transformed cells. The present results suggest that the use of theophylline might be useful for quantitative experiments on neoplastic transformation in cultures of normal human cells.