The comet assay as a tool in human biomonitoring exposure to antineoplastic drugs – A systematic review and meta-analysis

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research Pub Date : 2026-01-01 Epub Date: 2026-03-23 DOI:10.1016/j.mrrev.2026.108590

Carina Ladeira , Amaya Azqueta , Lisa Giovannelli , Goran Gajski , Marko Gerić , Anja Haveric , Helga Stopper , Ezgi Eyluel Bankoglu , Andrew Collins , Peter Møller

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Abstract

Antineoplastic agents are toxic compounds, generally used in the treatment of cancers, which are recognized as carrying a cancer development risk. In this systematic review and meta-analysis of human biomonitoring studies, we have assessed the effects of exposure to antineoplastic drugs on levels of DNA strand breaks in leukocytes, measured by the comet assay. Focusing on the application of the comet assay in human biomonitoring of occupational exposure to antineoplastic agents, we have analyzed 458 original research studies which used this assay, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA-ScR). The systematic review led to 23 studies, of which 20 studies met the criteria for inclusion in the meta-analysis. Using standardized mean difference and 95% confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to antineoplastic drugs (1.26, 95% CI: 0.78, 1.73). Results originate mainly from studies on healthcare workers, with only one study in an industrial setting. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.77, 95% CI: 1.00, 2.55) than studies from high-income countries (0.49, 95% CI: 0.09, 0.90). This difference between middle- and high-income countries may be attributable in part to differences in exposure levels or exposure assessment. Additionally, sensitivity analysis indicates that studies with moderate/high risk of comet assay measurement bias have higher effect size (2.07, 95% CI: 0.82, 3.31) than studies with low risk of bias (0.73, 95% CI: 0.34, 1.13); and that studies with high risk of exposure misclassification have higher effect size (1.47, 95% CI: 0.89, 2.06) than studies with low/moderate risk (0.13, 955 CI: −0.08, 0.33). Most studies have low/moderate risk of bias related to the comet assay procedure (15 out of 20 studies), absence of reporting the use of assay controls (1 out of 20 studies), blinded analysis of samples (7 out 20 studies); exposure assessment (16 out of 20 studies). In conclusion, this systematic review and meta-analysis shows that exposure to antineoplastic drugs is associated with increased levels of DNA strand breaks in human leukocytes.

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彗星试验作为人类抗肿瘤药物暴露生物监测工具的系统回顾和荟萃分析。

抗肿瘤药物是有毒化合物，通常用于治疗癌症，被认为具有癌症发展风险。在这项对人类生物监测研究的系统回顾和荟萃分析中，我们评估了暴露于抗肿瘤药物对白细胞中DNA链断裂水平的影响，这是通过彗星测定法测量的。重点关注彗星测定法在人类职业抗肿瘤药物暴露生物监测中的应用，我们根据系统评价和荟萃分析的首选报告项目（PRISMA-ScR）分析了458项使用该测定法的原始研究。系统评价纳入了23项研究，其中20项研究符合纳入meta分析的标准。使用标准化平均差和95%置信区间（CI），荟萃分析显示，暴露于抗肿瘤药物的受试者DNA链断裂水平增加（1.26,95% CI: 0.78, 1.73）。结果主要来自对卫生保健工作者的研究，只有一项研究是在工业环境中进行的。亚组分析表明，所有来自中等收入国家的综合研究的效应量（1.77,95% CI: 1.00, 2.55）高于来自高收入国家的研究（0.49,95% CI: 0.09, 0.90）。中等收入国家和高收入国家之间的这种差异可能部分归因于暴露水平或暴露评估的差异。此外，敏感性分析表明，彗星测定偏倚中/高风险研究的效应大小（2.07,95% CI: 0.82, 3.31）高于低偏倚风险研究（0.73,95% CI: 0.34, 1.13）；暴露错误分类高风险研究的效应量（1.47,95% CI: 0.89, 2.06）高于低/中等风险研究（0.13,955 CI: -0.08, 0.33）。大多数研究具有与彗星分析程序相关的低/中等偏倚风险（20项研究中有15项），没有报告使用分析对照（20项研究中有1项），对样本进行盲法分析（20项研究中有7项）；暴露评估（20项研究中的16项）。总之，本系统综述和荟萃分析表明，暴露于抗肿瘤药物与人类白细胞中DNA链断裂水平增加有关。

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来源期刊

Mutation Research-Reviews in Mutation Research 生物-毒理学

CiteScore

12.20

自引率

1.90%

发文量

审稿时长

15.7 weeks

期刊介绍： The subject areas of Reviews in Mutation Research encompass the entire spectrum of the science of mutation research and its applications, with particular emphasis on the relationship between mutation and disease. Thus this section will cover advances in human genome research (including evolving technologies for mutation detection and functional genomics) with applications in clinical genetics, gene therapy and health risk assessment for environmental agents of concern.