Raposa T, Várkonyi J
Cancer Detect Prev. 1987;10(1-2):141-51.
The genotoxicity of frequently used cytostatic agents was characterized by the enumeration of the sister chromatid exchanges (SCEs) induced by them in vivo in phytohemagglutinin-stimulated peripheral blood lymphocytes. Fifty-nine cancer patients undergoing and off chemotherapy are included in this study. The aim was to identify cytostatics according to their ability to alter the SCE frequency. Cytostatics with strong SCE-inducing ability (melphalan, cyclophosphamide, cyclophosphamide + vincristine + 5-fluorouracil, cyclophosphamide + vincristine + procarbazid + prednisolone) usually exhibited a longlasting SCE elevation. Cytosine arabinoside, hydroxyurea, vincristine, 5-fluorouracil, tamoxifen, and azathioprine did not induce SCEs. These data were compared with the leukemogenic potential of the same drugs in order to validate the relevance of SCE studies in man to signal carcinogenic hazards. It was found that over 80% of all secondary leukemias (collected from the world literature from 1930 to 1980) were preceded by the administration of cytotoxic compounds inducing long-lasting SCE elevation in lymphocytes. Only 3% of all secondary leukemias can be attributed to drugs not inducing SCEs in vivo in PHA-stimulated lymphocytes. This indicates that the lesions important for SCEs and secondary leukemias to emerge bear close biological similarities. Thus SCE studies can be used in selecting therapeutical protocols or new cytostatics with less carcinogenic potential to man.
常用细胞抑制剂的遗传毒性通过其在体内对植物血凝素刺激的外周血淋巴细胞诱导的姐妹染色单体交换（SCE）数量来表征。本研究纳入了59名正在接受化疗和已停止化疗的癌症患者。目的是根据细胞抑制剂改变SCE频率的能力来进行鉴定。具有较强SCE诱导能力的细胞抑制剂（美法仑、环磷酰胺、环磷酰胺+长春新碱+5-氟尿嘧啶、环磷酰胺+长春新碱+丙卡巴肼+泼尼松龙）通常会使SCE持续升高。阿糖胞苷、羟基脲、长春新碱、5-氟尿嘧啶、他莫昔芬和硫唑嘌呤不会诱导SCE。将这些数据与相同药物的致白血病潜力进行比较，以验证人体中SCE研究对于指示致癌风险的相关性。结果发现，所有继发性白血病（从1930年至1980年的世界文献中收集）中有超过80%在之前使用过能诱导淋巴细胞中SCE持续升高的细胞毒性化合物。在所有继发性白血病中，只有3%可归因于在体内PHA刺激的淋巴细胞中不诱导SCE的药物。这表明对于SCE和继发性白血病出现重要的损伤具有密切的生物学相似性。因此，SCE研究可用于选择对人类致癌潜力较小的治疗方案或新的细胞抑制剂。
