BUDR DEPENDENCE, MALIGNANCY, AND DIFFERENTIATION

进行了实验以测试是否存在可转基因的 5-溴脱氧尿苷(BrdU)对BrdU依赖性癌基因的调控作用 叙利亚仓鼠黑色素瘤品系的突变。在这条线上，转变了的 表型只有在高浓度的 BrdU。在一种相关的方法中，开始进行测试以寻找可转基因的 例如，具有遗传倾向的肿瘤的癌基因， 神经纤维瘤病(NF)。 染色体断裂事件与微扰的关系 在对人类脆性X基因的测试中分析了核苷酸代谢的 综合征，与精神发育迟滞有关，其表达 在培养的细胞中是由胸腺嘧啶核苷的扰动诱导的 生物合成。杂交种是从中国仓鼠与中国仓鼠的杂交中分离出来的。 男性脆性X患者的细胞和淋巴母细胞 综合症。杂交种在大约10%的人中表达了脆性部位 中期。 已分离出能抵抗5-氟尿嘧啶毒性作用的克隆 来自中国仓鼠的成纤维细胞。这些突变体中的原发病变 似乎是一种改变的CTP合成酶活性 对CTP的负性调节敏感。 对5-羟甲基脱氧尿苷(HmdU)进行了毒性实验. 已执行。发现hmdU的一个主要代谢产物是游离态。 无毒的嘧啶羟甲基尿嘧啶(HmUra)，也 对hmdU毒性的抗药性与增强的 将核苷降解为hmUra。(P)

Experiments were carried out to test for the presence of transfectable oncogenes controlled by 5-bromodeoxyuridine (BrdU) in BrdU-dependent mutants of a Syrian hamster melanoma line. In this line, the transformed phenotype is expressed only in the presence of high concentrations of BrdU. In a related approach, tests were begun to search for transfectable oncogenes in tumors with hereditary disposition, for example, neurofibromatosis (NF). The relationship between chromosomal breakage events and the perturbation of nucleotide metabolism was analyzed in tests on the human fragile X syndrome, which is associated with mental retardation and whose expression in cultured cells is induced by the perturbation of thymidine biosynthesis. Hybrids were isolated from crosses between Chinese hamster cells and lymphoblastoid cells from male patients with the fragile X syndrome. The hybrids expressed the fragile site in approximately 10% of metaphases. Clones resistant to the toxic effects of 5-fluorouracil have been isolated from Chinese hamster fibroblasts. A primary lesion in these mutants appears to be an altered CTP synthetase activity that is no longer sensitive to negative regulation by CTP. Experiments on the toxicity of 5-hydroxymethyldeoxyuridine (hmdU) were performed. It was found that a major metabolite of hmdU is the free pyrimidine hydroxymethyluracil (hmUra), which is not toxic, and also that resistance to hmdU toxicity is correlated with an increased ability to degrade the nucleoside to hmUra. (P)