Pilger A, Köhler I, Stettner H, Mader R M, Rizovski B, Terkola R, Diem E, Franz-Hainzl E, Konnaris C, Valic E, Rüdiger H W
Department of Occupational Medicine, University of Vienna, Austria.
Int Arch Occup Environ Health. 2000 Sep;73(7):442-8. doi: 10.1007/s004200000164.
Many antineoplastic drugs were found to have carcinogenic, mutagenic and teratogenic potential. The aim of this study was to carry out cytogenetic and internal dose monitoring of hospital pharmacy personnel regularly involved in the preparation of cytostatic agents, in order to test possible cytostatics-induced genotoxic effects due to occupational exposure under routine working conditions, and in cases of accidental contamination.
Platinum in whole blood and anthracyclines in plasma were measured to assess internal exposure to cytostatics. The level of cytogenetic damage was determined in peripheral blood lymphocytes with the micronucleus test and the sister chromatid exchange assay. Five series of monitoring were performed over a period of 2 years.
No significant differences in the mean frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) were found between occupationally exposed probands and controls (9.9 +/- 1.4 vs 10.1 +/- 1.2 SCEs/cell and 21.2 +/- 7.2 vs 23.3 +/- 7.5 MN/2000 binucleated (BN) cells, n = 16). Significant elevations of SCE or MN were detected in seven out of 12 cases of accidental contamination at the workplace, whereas no increase in platinum in blood and anthracyclines in plasma was observed in these probands. Two cases of non-reported contamination were identified by measurement of epirubicin in plasma. Smoking was found to increase the SCE significantly. No correlation between individual SCE scores and MN scores was observed.
Our findings support a transient increase in SCE or MN after relevant exposure to cytostatic drugs in cases of accidental contamination. The lack of significant differences in SCE and MN between hospital pharmacy personnel and unexposed controls, points to high standards of safety at the corresponding workplaces.
许多抗肿瘤药物被发现具有致癌、致突变和致畸潜力。本研究的目的是对经常参与细胞毒性药物配制的医院药房工作人员进行细胞遗传学和体内剂量监测，以检测在常规工作条件下职业暴露以及意外污染情况下，细胞毒性药物可能引起的遗传毒性效应。
测量全血中的铂和血浆中的蒽环类药物，以评估细胞毒性药物的体内暴露情况。通过微核试验和姐妹染色单体交换试验测定外周血淋巴细胞中的细胞遗传学损伤水平。在2年的时间里进行了5次监测。
职业暴露的受试者与对照组之间，姐妹染色单体交换（SCE）和微核（MN）的平均频率没有显著差异（分别为9.9±1.4与10.1±1.2个SCE/细胞，以及21.2±7.2与23.3±7.5个MN/2000个双核（BN）细胞，n = 16）。在12例工作场所意外污染病例中，有7例检测到SCE或MN显著升高，而这些受试者的血液中铂和血浆中蒽环类药物没有增加。通过测量血浆中的表柔比星，发现了2例未报告的污染情况。发现吸烟会显著增加SCE。未观察到个体SCE评分与MN评分之间的相关性。
我们的研究结果支持在意外污染情况下，接触细胞毒性药物后SCE或MN会短暂增加。医院药房工作人员与未暴露对照组之间SCE和MN没有显著差异，这表明相应工作场所的安全标准很高。
