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通过胞质分裂阻滞微核分析和单细胞凝胶电泳试验评估处理抗肿瘤药物的药剂师和护士淋巴细胞遗传损伤的随访研究。

Follow-up study of the genetic damage in lymphocytes of pharmacists and nurses handling antineoplastic drugs evaluated by cytokinesis-block micronuclei analysis and single cell gel electrophoresis assay.

作者信息

Maluf S W, Erdtmann B

机构信息

Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil.

出版信息

Mutat Res. 2000 Nov 20;471(1-2):21-7. doi: 10.1016/s1383-5718(00)00107-8.

DOI:10.1016/s1383-5718(00)00107-8
PMID:11080657
Abstract

A follow-up study was carried out 4 years after an initial evaluation of the micronucleus frequency in 10 healthy individuals who had been occupationally exposed to antineoplastic drugs in a Brazilian hospital. Upon the first evaluation, these 10 exposed individuals were compared with 10 non-exposed individuals matched for age, sex and smoking habits; the results revealed that the frequency of micronucleated lymphocytes in individuals exposed to antineoplastic drugs was significantly higher (P=0.038) than in controls. The frequency of dicentric bridges was also increased, although not significantly (P=0.0545). After the first analysis, the workers handling antineoplastic drugs were advised to modify their work schedule to limit exposure, and the number of workers in the group was increased from 10 to 12 individuals. In the follow-up study, 12 individuals from the same work area were assessed. In addition to micronucleus frequency, alkaline single cell gel electrophoresis was also used to monitor genetic hazard. This exposed group was compared to 12 non-exposed workers from the same hospital, matched for age, sex and smoking habits. In the follow-up study, no statistical difference was found between exposed workers and controls in terms of micronucleus and dicentric bridge frequency with the Mann--Whitney U-test (P=0.129 and 0.373, respectively). However, the mean value of SCGE analysis was significantly higher in the exposed group than in the controls (P=0.0006). Although the micronucleus analysis seems to be less sensitive to assess DNA damage, it detects chromosome aberrations and not just repairable DNA breakage and alkali-labile sites. Combination of the alkaline single cell gel electrophoresis and cytokinesis blocked micronucleus assay appears to be commendable to monitor populations chronically exposed to genotoxic agents.

摘要

在对巴西一家医院10名职业接触抗肿瘤药物的健康个体进行微核频率初步评估4年后,开展了一项随访研究。首次评估时,将这10名接触者与10名年龄、性别和吸烟习惯相匹配的未接触者进行比较;结果显示,接触抗肿瘤药物个体的微核淋巴细胞频率显著高于对照组(P=0.038)。双着丝粒桥的频率也有所增加,尽管不显著(P=0.0545)。首次分析后,建议处理抗肿瘤药物的工人调整工作时间表以限制接触,并将该组工人数量从10人增加到12人。在随访研究中,对来自同一工作区域的12名个体进行了评估。除了微核频率外,还使用碱性单细胞凝胶电泳来监测遗传危害。将这个接触组与同一家医院12名年龄、性别和吸烟习惯相匹配的未接触工人进行比较。在随访研究中,通过曼-惠特尼U检验发现,接触工人与对照组在微核和双着丝粒桥频率方面无统计学差异(分别为P=0.129和0.373)。然而,暴露组的SCGE分析平均值显著高于对照组(P=0.0006)。尽管微核分析在评估DNA损伤方面似乎不太敏感,但它检测的是染色体畸变,而不仅仅是可修复的DNA断裂和碱不稳定位点。碱性单细胞凝胶电泳和胞质分裂阻滞微核试验相结合似乎是监测长期接触遗传毒性剂人群的值得称赞的方法。

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