Ammenheuser M M, Ward J B, Whorton E B, Killian J M, Legator M S
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77550.
Mutat Res. 1988 Mar;204(3):509-20. doi: 10.1016/0165-1218(88)90045-6.
An autoradiographic assay for 6-thioguanine-resistant (TGr) lymphocytes was used to determine the frequency of in vivo derived variant T lymphocytes in peripheral blood from multiple sclerosis (MS) patients treated with monthly intravenous infusions of 750 mg/m2 of cyclophosphamide (CP). To analyze the time-course of response to CP, the MS patients were studied prospectively. Samples were obtained from the patients before the beginning of CP therapy, 4-5 times during the course of treatment, and, finally, 2 or 3 months after the completion of therapy. 2 weeks after the first CP infusion, the variant frequencies (Vfs) of the MS patients were significantly increased (p less than 0.05) above their pre-treatment values, but by 4 weeks following the first CP infusion the Vfs had fallen to normal or near-normal levels. After subsequent treatments, the frequencies of variant TGr cells were again higher than pre-treatment Vfs. However, within 7-13 weeks after the cessation of CP therapy, the Vfs of all subjects had returned to normal levels. The transient nature of the response indicates rapid in vivo selection against CP-induced TGr mutant cells. The mean pre-treatment Vf of the 4 MS patients who were cigarette smokers was 6.56 X 10(-6) which was significantly greater (p less than 0.05) than the mean Vf (1.52 X 10(-6) of the 4 MS patients who were non-smokers. The mean Vf from 8 assays of healthy non-smokers was 1.92 X 10(-6).
采用一种针对6-硫鸟嘌呤抗性（TGr）淋巴细胞的放射自显影测定法，来确定接受每月静脉输注750 mg/m²环磷酰胺（CP）治疗的多发性硬化症（MS）患者外周血中体内衍生的变异T淋巴细胞的频率。为了分析对CP反应的时间进程，对MS患者进行了前瞻性研究。在CP治疗开始前、治疗过程中4 - 5次以及治疗完成后2或3个月从患者身上采集样本。首次CP输注后2周，MS患者的变异频率（Vf）显著高于治疗前水平（p小于0.05），但在首次CP输注后4周，Vf已降至正常或接近正常水平。后续治疗后，变异TGr细胞的频率再次高于治疗前的Vf。然而，在CP治疗停止后7 - 13周内，所有受试者的Vf均恢复到正常水平。这种反应的短暂性表明体内对CP诱导的TGr突变细胞进行了快速选择。4名吸烟的MS患者治疗前的平均Vf为6.56×10⁻⁶，显著高于4名不吸烟的MS患者的平均Vf（1.52×10⁻⁶）（p小于0.05）。8名健康不吸烟者的平均Vf为1.92×10⁻⁶。
