Cadmium exposure and DNA damage (genotoxicity): a systematic review and meta-analysis

Abstract

Existing literature suggests an association between chronic cadmium (Cd) exposure and the induction of DNA damage and genotoxicity. However, observations from individual studies are inconsistent and conflicting. Therefore current systematic review aimed to pool evidence from existing literature to synthesize quantitative and qualitative corroboration on the association between markers of genotoxicity and occupational Cd exposed population. Studies that evaluated markers of DNA damage among occupationally Cd-exposed and unexposed workers were selected after a systematic literature search. The DNA damage markers included were chromosomal aberrations (chromosomal, chromatid, sister chromatid exchange), Micronucleus (MN) frequency in mono and binucleated cells (MN with condensed chromatin, lobed nucleus, nuclear buds, mitotic index, nucleoplasmatic bridges, pyknosis, and karyorrhexis), comet assay (tail intensity, tail length, tail moment, and olive tail moment), and oxidative DNA damage (8-hydroxy-deoxyguanosine). Mean differences or standardized mean differences were pooled using a random-effects model. The Cochran-Q test and I² statistic were used to monitor heterogeneity among included studies. Twenty-nine studies with 3080 occupationally Cd-exposed and 1807 unexposed workers were included in the review. Cd among the exposed group was higher in blood [4.77 μg/L (−4.94–14.48)] and urine samples [standardized mean difference 0.47 (0.10–0.85)] than in the exposed group. The Cd exposure is positively associated with higher levels of DNA damage characterized by increased frequency of MN [7.35 (−0.32–15.02)], sister chromatid exchange [20.30 (4.34–36.26)], chromosomal aberrations, and oxidative DNA damage (comet assay and 8OHdG [0.41 (0.20–0.63)]) compared to the unexposed. However, with considerable between-study heterogeneity. Chronic Cd exposure is associated with augmented DNA damage. However, more extensive longitudinal studies with adequate sample sizes are necessary to assist the current observations and promote comprehension of the Cd’s role in inducing DNA damage.

Prospero Registration ID: CRD42022348874.

Keywords:

• Cadmium
• occupational exposure
• DNA damage
• micronuclei
• sister chromatid exchange
• chromosomal aberrations
• comet assay
• oxidative DNA damage

Acknowledgements

The authors are gratefully thankful to the external reviewers selected by the journal, who are anonymous to the authors, and whose comments and suggestions are enormously valuable in revising and structuring the manuscript. The authors wish to acknowledge the Director of each institute for their timely support and internal review process, to submit the manuscript. All authors agreed on the final version of the manuscript and are accountable for all aspects of the work related to the accuracy and integrity of each part of the work, which is appropriately investigated and resolved.

Declaration of interest

All authors report no conflict of interest, and the manuscript was written as part of the author’s normal employment. The affiliation of the authors is as mentioned on the cover page, and the manuscript is the outcome of the individual author’s expertise in the current topic over many years. All authors were involved in the article preparation and review process, and no individuals other than the cited authors were involved in any manuscript work. The authors have not participated in and do not anticipate participation in any legal, regulatory, or advocacy proceedings related to the contents of the paper.

Supplemental material

Supplemental material for this article is available online here.

Data availability statement

All the relevant data is included in the Supplementary Material.