Cavallo Delia, Ursini Cinzia Lucia, Perniconi Barbara, Francesco Arianna Di, Giglio Margherita, Rubino Federico Maria, Marinaccio Alessandro, Iavicoli Sergio
Department of Occupational Medicine, ISPESL-National Institute for Occupational Safety and Prevention, Via Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy.
Mutat Res. 2005 Nov 10;587(1-2):45-51. doi: 10.1016/j.mrgentox.2005.07.008. Epub 2005 Oct 3.
The continuous introduction of new antineoplastic drugs and their use as complex mixture emphasize the need to carry out correct health risk assessment. The aim of this study was to evaluate genotoxic effects of antineoplastic drugs in nurses (n=25) and pharmacy technicians (n=5) employed in an oncology hospital. The nurses administered antineoplastic drugs in the day-care hospital (n=12) and in the wards (n=13), and pharmacy technicians prepared the drugs in the central pharmacy. We performed the micronucleus (MN) test with lymphocytes and exfoliated buccal cells and conducted traditional analysis of chromosomal aberrations (CA). Thirty healthy subjects were selected as controls. Monitoring of surface contamination with cyclophosphamide, 5-fluorouracil, ifosfamide, cytarabine, and gemcitabine showed the presence of detectable levels only for cyclophosphamide, 5-fluorouracil and ifosfamide. In addition, we measured the 5-fluorouracil metabolite alpha-F-betaalanine in the urine of all subjects and found significant concentrations only in 3 out of 25 nurses. The micronucleus assay with lymphocytes did not show significant differences between exposed and control groups, while the same test with exfoliated buccal cells found higher values in nurses administering antineoplastic drugs than in pharmacy employees. In the CA analysis, we detected in exposed groups a significant increase (about 2.5-fold) of structural CA, particularly breaks (up to 5.0-fold). Our results confirm the genotoxic effect of antineoplastic drugs in circulating blood lymphocytes. Moreover, in exfoliated buccal cells the data show more consistent genetic damage induced during administration of the antineoplastic drugs than during their preparation. The data also stress the use of this non-invasive sampling, to assess occupational exposure to mixture of chemicals at low doses.
新型抗肿瘤药物的不断推出及其作为复方制剂的使用,凸显了进行正确健康风险评估的必要性。本研究旨在评估肿瘤医院中护士(n = 25)和药剂师(n = 5)接触抗肿瘤药物的遗传毒性效应。护士在日间护理医院(n = 12)和病房(n = 13)给药,药剂师在中心药房配制药物。我们对淋巴细胞和脱落的颊黏膜细胞进行了微核(MN)试验,并进行了传统的染色体畸变(CA)分析。选取30名健康受试者作为对照。对环磷酰胺、5-氟尿嘧啶、异环磷酰胺、阿糖胞苷和吉西他滨的表面污染监测显示,仅环磷酰胺、5-氟尿嘧啶和异环磷酰胺存在可检测水平。此外,我们测量了所有受试者尿液中的5-氟尿嘧啶代谢产物α-F-β-丙氨酸,仅在25名护士中的3人发现有显著浓度。淋巴细胞微核试验在暴露组和对照组之间未显示出显著差异,而脱落颊黏膜细胞的相同试验发现,给药的护士中的微核值高于药剂师。在CA分析中,我们在暴露组中检测到结构CA显著增加(约2.5倍),尤其是断裂(高达5.0倍)。我们的结果证实了抗肿瘤药物对循环血淋巴细胞的遗传毒性作用。此外,在脱落的颊黏膜细胞中,数据显示在抗肿瘤药物给药过程中诱导的遗传损伤比其配制过程中更一致。数据还强调了使用这种非侵入性采样来评估低剂量化学混合物的职业暴露。