Lasso de la Vega M C, Terradez P, Obrador E, Navarro J, Pellicer J A, Estrela J M
Departamento de Fisiología, Facultad de Medicina, Valencia, Spain.
Biochem J. 1994 Feb 15;298 ( Pt 1)(Pt 1):99-105. doi: 10.1042/bj2980099.
We have investigated the effect of extracellular ATP on tumour-cell proliferation and GSH levels in Ehrlich-ascites-tumour-bearing mice. After daily administration of exogenous ATP (1 mmol/kg) during 7 days, we found a 56% inhibition of tumour growth, precisely when controls show the highest rates of cell proliferation and the highest levels of GSH. This effect is accompanied by a decrease in GSH content in the tumour, but not in normal tissues. The decrease in GSH concentration within the cancer cells is associated with a decrease in gamma-glutamylcysteine synthetase activity and in protein synthesis. Growth inhibition is mediated by generation of extracellular adenosine, which subsequently increases intracellular levels of ATP and decreases intracellular levels of UTP in the cancer cells. Our results suggest that inhibition of tumour growth by ATP is due to an adenosine-dependent pyrimidine starvation effect.
我们研究了细胞外ATP对荷艾氏腹水瘤小鼠肿瘤细胞增殖及谷胱甘肽（GSH）水平的影响。在连续7天每日给予外源性ATP（1 mmol/kg）后，我们发现肿瘤生长受到56%的抑制，而此时对照组的细胞增殖速率最高且GSH水平也最高。这种效应伴随着肿瘤中GSH含量的降低，但正常组织中未出现此现象。癌细胞内GSH浓度的降低与γ-谷氨酰半胱氨酸合成酶活性及蛋白质合成的降低有关。生长抑制是由细胞外腺苷的生成介导的，随后癌细胞内ATP水平升高而UTP水平降低。我们的结果表明，ATP对肿瘤生长的抑制作用是由于腺苷依赖性嘧啶饥饿效应。
