Palmer R G, Smith-Burchnell C A, Pelton B K, Hylton W, Denman A M
Connective Tissue Diseases Research Group, Clinical Research Centre, Harrow, Middlesex, United Kingdom.
Arthritis Rheum. 1988 Jun;31(6):757-61. doi: 10.1002/art.1780310609.
By cloning T cells, mutations at the hypoxanthine-guanine phosphoribosyltransferase locus were quantified in peripheral blood lymphocytes of 12 patients with connective tissue diseases receiving long-term cyclophosphamide. Frequency of mutation was higher than in control subjects and was related to the duration of therapy; therefore, some cells with mutations are long-lived, and these cells accumulate in the peripheral circulation. Mutation frequency was also independently related to age. The results indicate that even low doses of cyclophosphamide are mutagenic and may explain, in part, why these patients are at risk of drug-induced malignancy.
通过克隆T细胞，对12名接受长期环磷酰胺治疗的结缔组织病患者外周血淋巴细胞中次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶基因座的突变进行了定量分析。突变频率高于对照组，且与治疗持续时间相关；因此，一些带有突变的细胞寿命较长，这些细胞在外周循环中积累。突变频率还与年龄独立相关。结果表明，即使是低剂量的环磷酰胺也具有致突变性，这在一定程度上可以解释为什么这些患者有发生药物诱导性恶性肿瘤的风险。
