Naguib F N, Niedzwicki J G, Iltzsch M H, Wiemann M C, el Kouni M H, Cha S M
Division of Biology and Medicine, Brown University, Providence, RI 02912.
Leuk Res. 1987;11(10):855-61. doi: 10.1016/0145-2126(87)90129-9.
Effects of a 7-day treatment with the maturational agents DMF and sodium butyrate on enzymes of pyrimidine metabolism, growth rate and cell maturation were assessed in 5 human tumor cell lines, ARH-77 (myeloma), K-562 (chronic myeloid leukemia), KG-1 (myeloid leukemia), HL-60 (promyelocytic leukemia) and RWLy-1 (non-Hodgkin's lymphoma). DMF lengthened the doubling times of all five cell lines while sodium butyrate lengthened only those of K-562, HL-60 and RWLy-1. Full maturation was induced only in HL-60 by either agent and in K-562 by butyrate. Exposure resulted in a decreased activity of the anabolic enzyme orotate phosphoribosyltransferase (EC 2.4.2.10) and increased activities of the catabolic enzymes thymidine phosphorylase (EC 2.4.2.4) and dihydrouracil dehydrogenase (EC 1.3.1.2). Changes in the amphibolic enzyme, uridine phosphorylase (EC 2.4.2.3) did not follow any apparent pattern. This study indicates that the pattern of pyrimidine metabolism differs between the differentiated and slowly growing, and undifferentiated rapidly growing counterpart of several human tumors, suggesting that enzymes of pyrimidine metabolism can be used as markers for cellular growth and/or maturity.
在5种人类肿瘤细胞系ARH - 77（骨髓瘤）、K - 562（慢性髓性白血病）、KG - 1（髓性白血病）、HL - 60（早幼粒细胞白血病）和RWLy - 1（非霍奇金淋巴瘤）中，评估了成熟剂二甲基富马酸（DMF）和丁酸钠进行为期7天的治疗对嘧啶代谢酶、生长速率和细胞成熟的影响。DMF延长了所有5种细胞系的倍增时间，而丁酸钠仅延长了K - 562、HL - 60和RWLy - 1的倍增时间。两种药物仅在HL - 60中诱导了完全成熟，丁酸钠在K - 562中诱导了完全成熟。暴露导致合成代谢酶乳清酸磷酸核糖基转移酶（EC 2.4.2.10）的活性降低，分解代谢酶胸苷磷酸化酶（EC 2.4.2.4）和二氢尿嘧啶脱氢酶（EC 1.3.1.2）的活性增加。兼性代谢酶尿苷磷酸化酶（EC 2.4.2.3）的变化没有遵循任何明显模式。这项研究表明，几种人类肿瘤的分化且生长缓慢的细胞与未分化且生长迅速的细胞之间嘧啶代谢模式不同，这表明嘧啶代谢酶可用作细胞生长和/或成熟的标志物。
