Selective high metabolic lability of uridine triphosphate in response to glucosamine feeding of untransformed and polyoma virus-transformed hamster fibroblasts.

Abstract

AbstractDerepression of hexose transport in a line of Syrian hamster fibroblasts (Nil) and polyoma‐transformed (PyNil) hamster fibroblasts is obtained when cells are either starved for glucose or fed with fructose as the only hexose source. D‐glucosamine feeding of these cells does not alter the repressed state with regard to hexose transport. High, derepressed rates of galactose transport were changed to low, repressed rates, within 18 hours of refeeding glucose‐starved cells with D‐glucosamine as the only hexose source. Nil and PyNil cells, when cultured in the presence of D‐glucosamine, undergo rapid reductions in total cellular uridine 5′‐triphosphate (UTP) pool sizes. By contrast, the total cellular pools of adenosine 5′‐triphosphate, guanosine 5′‐triphosphate, and cytosine 5′‐triphosphate (ATP, GTP, and CTP) were only moderately affected by the treatment of the cells with glucosamine. The metabolic drain of the UTP pools in PyNil cells was much more pronounced than in the untransformed cells. The larger and more rapid metabolic lability of UTP pools in the transformed cells may be the primary reason for the selective toxicity of glucosamine on tumor cells. A comparison of the effects of glucosamine on hexose‐starved Nil and PyNil cells demonstrated that only the untransformed cells were able to utilize glucosamine to increase the hexose starvation‐depleted pools of all nucleoside triphosphates. Accumulation of UDP‐glucosamine and UDP‐N‐acetylglucosamine followed the reduction in the UTP pools. Inhibition of protein synthesis by cycloheximide during glucosamine feeding led to higher levels of UDP‐glucosamine and UDP‐N‐acetylglucosamine accumulation. It is suggested that the drain of UTP pools during glucosamine treatment proceeds through the formation of the UDP‐aminosugars which turn over due to the action of intracellular UDP‐aminosugar pyrophosphatase activities.