The comet assay as a tool in human biomonitoring of exposure to heavy metals: a systematic review and meta-analysis

Exposure to heavy metals such as lead, arsenic, and chromium is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed the effects of heavy metal exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. We distinguish between traditional toxic metals (lead), semi-metals/metalloids (arsenic), transition metals (chromium), and other heavy metals. The literature search led to 66 studies, which were assessed by 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 lead (1.99, 95 % CI: 1.47, 2.51), arsenic (1.36, 95 % CI: 0.94, 1.77), chromium/welding fume (2.03, 95 % CI: 1.48, 2.57), and other heavy metals (0.81, 95 % CI: 0.45, 1.18). Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.99, 95 % CI: 1.63, 2.35) than studies from high-income countries (0.81, 95 % CI: 0.37, 1.26). The lower effect size in high-income countries may be due to differences in exposure levels, related to stricter regulation of emissions or more awareness/use of personal protective equipment in the working environment. Sensitivity analysis does not unequivocally link effect size to comet assay measurement bias, inferred by insufficient information on comet assay procedures, missing assay controls, non-blinded analysis of samples, or exposure misclassification. In conclusion, this systematic review and meta-analysis shows that exposure to heavy metals - lead, arsenic, and chromium - is associated with increased levels of DNA strand breaks in human leukocytes.

Description

This work was supported by the affiliated institutions, European Regional Development Fund project KK.01.1.1.02.0007 (Rec-IMI), the Croatian Science Foundation (HUMNap project #1192), the Horizon Europe (EDIAQI project #101057497), the European Union—Next Generation EU 533–03–23–0006 (BioMolTox), and the International Comet Assay Working Group (ICAWG).

Keywords

Biomonitoring DNA damage Genotoxicity biomarkers Meta-analysis Occupational exposure Transition metals

URI

http://hdl.handle.net/10400.21/22313

Citation

Møller P, Bankoglu EE, Stopper H, Gajski G, Gerić M, Ladeira C, et al. The comet assay as a tool in human biomonitoring of exposure to heavy metals: a systematic review and meta-analysis. Mutat Res Rev Mutat Res. 2025;796:108567.