Aristizabal-Pachon Andres Felipe, Castillo Willian Orlando
1Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Carrera 7 # 43-82, Bogota, D.C. Colombia.
2Department of Biology, Faculty of Natural Sciences, Exact and Education, University of Cauca, Popayán, Colombia.
Toxicol Res. 2019 Dec 2;36(1):29-36. doi: 10.1007/s43188-019-00003-7. eCollection 2020 Jan.
During the last years, several reports have provided evidence about adverse health effects on personal involved in Antineoplastic Drugs (ANPD) handling. ANPD has the ability to bind DNA, thus produce genotoxic damage. In this way, XRCC1 and XRCC3 proteins are necessary for efficient DNA repair and polymorphisms in this genes can be associated with an individual response to ANPD exposure. Therefore, the aim of this study was to evaluate genetic damage of occupational exposure to antineoplastic drugs and the possible effect of and polymorphisms in oncology employees from Bogotá, Colombia. Peripheral blood samples were obtained from 80 individuals, among exposed workers and healthy controls. The comet assay and Cytokinesis-block micronucleus cytome assay was performed to determinate genetic damage. From every sample DNA was isolated and genotyping for (Arg194Trp, Arg280His and Arg399Gln) and (Thr241Met) SNPs by PCR-RFLP. The exposed group showed a significant increase of comet assay results and micronucleus frequency, compared with unexposed group. It was observed a gender, exposure time and workplace effect on comet assay results. Our results showed no significant associations of comet assay results and micronucleus frequency with either genotype, allele, nor haplotype of and SNPs. The results suggest that occupational exposure to ANPD may lead to genotoxic damage and even be a risk to human health. To our knowledge, this is the first study to assess the genotoxic damage of occupational exposure to APND in South America.
在过去几年中,几份报告提供了证据,表明参与抗肿瘤药物(ANPD)处理的人员存在健康不良影响。ANPD能够结合DNA,从而产生基因毒性损伤。通过这种方式,XRCC1和XRCC3蛋白对于有效的DNA修复是必需的,并且这些基因中的多态性可能与个体对ANPD暴露的反应相关。因此,本研究的目的是评估哥伦比亚波哥大肿瘤学员工职业接触抗肿瘤药物的遗传损伤以及XRCC1和XRCC3多态性的可能影响。从80名个体中采集外周血样本,包括暴露工人和健康对照。进行彗星试验和胞质分裂阻滞微核细胞试验以确定遗传损伤。从每个样本中分离DNA,并通过PCR-RFLP对XRCC1(Arg194Trp、Arg280His和Arg399Gln)和XRCC3(Thr241Met)单核苷酸多态性进行基因分型。与未暴露组相比,暴露组的彗星试验结果和微核频率显著增加。观察到性别、暴露时间和工作场所有彗星试验结果有影响。我们的结果显示,彗星试验结果和微核频率与XRCC1和XRCC3单核苷酸多态性的基因型、等位基因或单倍型均无显著关联。结果表明,职业接触ANPD可能导致基因毒性损伤,甚至对人类健康构成风险。据我们所知,这是南美洲第一项评估职业接触APND的基因毒性损伤的研究。