Nicklas J A, O'Neill J P, Hunter T C, Falta M T, Lippert M J, Jacobson-Kram D, Williams J R, Albertini R J
Vermont Regional Cancer Center, Burlington.
Mutat Res. 1991 Sep-Oct;250(1-2):383-96. doi: 10.1016/0027-5107(91)90195-t.
The hprt T-lymphocyte cloning assay, which detects mutations occurring in vivo in humans, has been used to examine mutants induced in patients receiving radioimmunoglobulin therapy (RIT) for cancer. Samples from 13 patients before treatment (controls) and 15 samples from 12 patients after treatment were studied for both mutant frequencies and molecular changes in the hprt mutant T-cell clones. Patients were studied up to 48 months after treatment. Post-RIT patients showed increased mutant frequencies as compared to pre-treatment values. T-cell receptor (TCR) gene analysis of mutant T-cell clones demonstrated that 84% arose independently, both pre- and post-treatment, which is the same proportion as seen in normal individuals. However, several individuals did show large sets of mutants with the same TCR gene rearrangement patterns. Molecular analysis of mutants demonstrated a greater proportion of mutations with hprt gene changes on Southern blots after RIT treatment than before (40% versus 20%). RIT increases the proportion of mutations with total rather than partial gene deletions or other gross structural changes compared to normal individuals or pre-treatment patients. These studies are defining the spectrum for radiation-induced hprt gene mutations in vivo in human T-lymphocytes.
次黄嘌呤磷酸核糖转移酶（hprt）T淋巴细胞克隆试验可检测人体内发生的突变，已被用于研究接受癌症放射免疫球蛋白疗法（RIT）的患者体内诱导产生的突变体。对13例治疗前患者的样本（对照组）以及12例治疗后患者的15个样本进行了研究，分析hprt突变T细胞克隆的突变频率和分子变化。对患者进行了长达48个月的随访。与治疗前相比，接受RIT治疗后的患者突变频率增加。对突变T细胞克隆的T细胞受体（TCR）基因分析表明，84%的突变体在治疗前和治疗后都是独立产生的，这一比例与正常个体相同。然而，有几个个体确实出现了大量具有相同TCR基因重排模式的突变体。对突变体的分子分析表明，与治疗前相比，RIT治疗后Southern印迹上hprt基因发生变化的突变比例更高（40%对20%）。与正常个体或治疗前患者相比，RIT增加了具有全基因缺失而非部分基因缺失或其他总体结构变化的突变比例。这些研究正在确定人类T淋巴细胞体内辐射诱导的hprt基因突变谱。
