PTERIDINE METABOLISM AND TRANSPORT IN MALIGNANT CELLS

临床观察表明，蝶啶代谢的改变与 将蝶啶排泄到疾病，包括恶性肿瘤、病毒性 感染，细胞免疫系统的普遍激活，以及 艾滋病 为了帮助理解这些意见，本提案寻求 研究人类细胞中蝶啶生物化学的某些领域， 系统. 特别地，旨在测定蝶啶含量， 的细胞提取物和培养基;调查的性质， 控制这些衍生物流入和流出的转运系统; 并确定二氢蝶啶和 二氢叶酸还原酶在控制蝶啶代谢中的作用 的 研究将使用人类淋巴细胞和各种 人来源的恶性细胞系，包括CEM、WIL 2、HL 60和K562。 酶的研究将采用从大鼠肝脏分离的蛋白质， 人力资源。 特别重要的是， 可调节排泄的蝶啶类。 放射性标记 将使用蝶啶和叶酸来确定 分泌的化合物，因为蝶啶生物合成或 可能与叶酸降解有关。 蝶啶的性质 运输系统将说明这些是否提供了一个更清晰的画面， 某些细胞系统的蝶啶排泄产物是否可能 通过摄取或表面结合至其他细胞而具有调节意义 类型 通过这些手段，它旨在扩大对 蝶啶在人类细胞系统中发挥作用，从而确定 可以利用先前记录的临床观察结果， 无论是诊断上还是治疗上 （一）

Clinical observations have linked altered pteridine metabolism and enhanced excretion of pteridines to diseases, which include malignancies, viral infections, generalized activation of the cellular immune system, and AIDS. In order to help understand these observations, this proposal seeks to investigate certain areas of pteridine biochemistry in human cell systems. In particular, it is intended to determine the pteridine content of cell extracts and culture media; to investigate the properties of the transport system which controls the influx and efflux of these derivatives; and to determine the relative roles played by dihydropteridine and dihydrofolate reductases in controlling pteridine metabolism. The investigations will be carried out using human lymphocytes and a variety of malignant cell lines of human origin including CEM, WIL2, HL60, and K562. The enzyme studies will employ the isolated proteins from rat liver and human sources. Of particular importance will be the identification of pteridines subject to modulated excretion. Radioactively labelled pteridines and folates will be employed to establish the origin of the secreted compounds since intermediates of both pteridine biosynthesis or folate degradation could be involved. The properties of the pteridine transport system will illustrate whether these provide a clearer picture of whether the pteridine excretion products of certain cell systems might be of regulatory significance by uptake or surface binding to other cell types. By these means, it is intended to expand the understanding of pteridine function in human cell systems and, thereby, determine whether previously documented clinical observations can be exploited either diagnostically or therapeutically. (A)