Goldberg M T, Tackaberry L E, Hardy M H, Noseworthy J H
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Canada.
Arch Toxicol. 1990;64(2):116-21. doi: 10.1007/BF01974396.
The toxic effect of cyclophosphamide on the proliferative cell population of hair follicles plucked from the human scalp was examined by the in vivo nuclear aberration assay. Patients participating in an independent clinical trial received oral low dose cyclophosphamide, intravenous high dose cyclophosphamide or oral placebo treatment. The percent of cells with nuclear aberrations (indicating apoptosis, a special form of cell death) and the percent of mitotic cells, in the hair matrix, were calculated for each patient before treatment and at several time points following cyclophosphamide or placebo treatment. The mean percentages of nuclear aberrations in both the treated Low dose and High dose cyclophosphamide patients were significantly higher than those for the pre-treatment and Placebo patients. The nuclear aberrations in hair follicle cells increased from pre-treatment (and Placebo) to treated Low dose and finally to treated High dose patients. The average percentage for pre-treatment samples from all patients was 0.06 +/- 0.03 SE. For 1 week and 1 month samples from Low dose patients it was 0.35 +/- 0.08 SE, and for combined 2,3 and 4 day samples from High dose patients it was 1.08 +/- 0.12 SE. Cyclophosphamide also had a significant effect on mitosis. A decrease in mitotic activity was observed at 1 month following the initial low dose cyclophosphamide treatment and at 24 +/- 2 h following each of the first two high dose cyclophosphamide treatments. The observed increase in nuclear aberrations following low dose as well as high dose cyclophosphamide suggests that it is feasible to use the nuclear aberration assay for in vivo human genotoxicity testing, using proliferating hair follicle cells.
通过体内核畸变试验，研究了环磷酰胺对从人头皮拔出的毛囊增殖细胞群体的毒性作用。参与一项独立临床试验的患者接受口服低剂量环磷酰胺、静脉注射高剂量环磷酰胺或口服安慰剂治疗。在治疗前以及环磷酰胺或安慰剂治疗后的几个时间点，计算每位患者毛囊基质中具有核畸变的细胞百分比（表明凋亡，一种特殊形式的细胞死亡）以及有丝分裂细胞的百分比。低剂量和高剂量环磷酰胺治疗患者的核畸变平均百分比均显著高于治疗前和安慰剂治疗患者。毛囊细胞中的核畸变从治疗前（和安慰剂组）到低剂量治疗患者，最终到高剂量治疗患者逐渐增加。所有患者治疗前样本的平均百分比为0.06±0.03标准误。低剂量患者1周和1个月样本的该百分比为0.35±0.08标准误，高剂量患者第2、3和4天样本合并后的该百分比为1.08±0.12标准误。环磷酰胺对有丝分裂也有显著影响。在最初低剂量环磷酰胺治疗后1个月以及前两次高剂量环磷酰胺治疗后每一次的24±2小时，观察到有丝分裂活性降低。低剂量和高剂量环磷酰胺后观察到的核畸变增加表明，使用增殖的毛囊细胞进行体内人类遗传毒性测试，采用核畸变试验是可行的。
