Selective inhibition by benzaldehyde of the uptake of nucleosides and sugar into simian virus 40-transformed cells

Abstract

The effects of benzaldehyde, which has been found in figs as a carcinostatic element, were studied on the uptake of nucleosides, 2-deoxy-D-glucose, and amino acids into simian virus 40-transformed rat fibroblast cells (SV40-transformed cells) and into the parent normal cells (normal cells). Benzaldehyde, at the concentrations of 25 to 100 microgram/ml at which the selective growth inhibition against SV40-transformed cells was revealed, markedly inhibited the uptake of thymidine, other nucleosides, and 2-deoxy-D-glucose into SV40-transformed cells without any significant inhibition of the uptake of these compounds into normal cells. The uptake of amino acids into both transformed and normal cells was not inhibited by benzaldehyde. Selectively cytotoxic benzaldehyde-related compounds such as 4-nitrobenzaldehyde, 4-acetaminobenzaldehyde, thiophene-3-carboxaldehyde, etc., showed a similar inhibitory effect on thymidine uptake. The deprivation of glucose from the incubation medium strikingly diminished the inhibitory effect of benzaldehyde on the uptake of thymidine and 2-deoxy-D-glucose into SV40-transformed cells. The intracellular adenosine 5'-triphosphate level of SV40-transformed cells was reduced to less than one-half by treatment with benzaldehyde (50 microgram/ml) in glucose-containing medium. This effect was not observed in glucose-free medium. Treatment with benzaldehyde caused no change of the intracellular adenosine 5'-triphosphate level of normal cells. Based on the above results, the selective cytotoxicity of benzaldehyde was attributed to the reduction of intracellular adenosine 5'-triphosphate level of transformed cells, accompanied by the poor uptake of thymidine, glucose, etc., into SV40-transformed cells.