{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:29:58Z","timestamp":1787671798620,"version":"build-2736575974"},"reference-count":144,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Global antibiotic consumption continues to rise across pediatric and adult populations, while the genotoxic consequences of host eukaryotic exposure remain less systematically characterized than the parallel problem of antimicrobial resistance. Several lines of evidence, from molecular cytogenetics, redox biology, and systems toxicology, now permit a more mechanistically resolved synthesis of antibiotic-induced genome stress than was previously possible, although a substantial fraction of this evidence is preclinical and warrants cautious clinical extrapolation. This narrative review evaluates the molecular mechanisms, cytogenetic biomarkers, and translational implications of antibiotic-induced genotoxicity, with a primary focus on six clinically prominent classes (fluoroquinolones, nitroimidazoles, aminoglycosides, macrolides, \u03b2-lactams, and tetracyclines) and a brief extension to glycopeptides and glycylcyclines. We organize the evidence around three convergent mechanistic axes rather than around individual drugs. Accumulating evidence supports three intersecting off-target axes: (i) eukaryotic topoisomerase II interference, principally documented for fluoroquinolones; (ii) mitochondrial dysfunction, reflecting the evolutionary kinship between the mitoribosome and bacterial ribosomes; and (iii) inflammation-coupled redox stress, often amplified by microbiome perturbation. These pathways converge on a common spectrum of DNA lesions\u2014including double-strand breaks, oxidatively modified bases, replication-fork stalling, and chromosomal mis-segregation) detected by complementary assays (CBMN-Cyt, comet, \u03b3H2AX, and oxidative and mitochondrial biomarkers). Pediatric, pregnant, geriatric, and oncology populations may represent biologically distinct susceptibility strata, although direct human evidence for several of these inferences remains limited. Causal inference is constrained by infection as a confounder, frequent use of supratherapeutic in vitro concentrations, reliance on immortalized cell lines that may not recapitulate primary-cell repair capacity, inter-laboratory variability across cytogenetic assays, and a marked scarcity of pediatric and pregnancy biomonitoring data. Most existing positive signals derive from preclinical models; clinically validated long-term outcomes, particularly carcinogenic endpoints, remain inconsistently demonstrated for most antibiotic classes outside metronidazole. Antibiotic-induced genotoxicity appears to be a measurable and mechanistically tractable dimension of drug safety, though its clinical magnitude in real-world exposure scenarios requires further investigation. Integrating multi-omics, microphysiological systems, single-cell genotoxicology, and AI-assisted prediction may improve risk resolution, particularly in vulnerable populations. We argue that antimicrobial stewardship discussions should consider host genome integrity alongside resistance, while remaining mindful that the mechanistic case currently outpaces clinical-endpoint validation.<\/jats:p>","DOI":"10.3390\/ijms27167460","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"7460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibiotic-Induced Genotoxicity: Molecular Mechanisms, Cytogenetic Damage, and Implications for Human Health"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2036-6929","authenticated-orcid":false,"given":"Ahmet Ali","family":"Berber","sequence":"first","affiliation":[{"name":"Vocational School of Health Services, \u00c7anakkale Onsekiz Mart University, 17100 Canakkale, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Sakarya University, 54050 Sakarya, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3340-598X","authenticated-orcid":false,"given":"\u015eefika Nur","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3917-6412","authenticated-orcid":false,"given":"Nihan Ak\u0131nc\u0131","family":"Kenano\u011flu","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, \u00c7anakkale Onsekiz Mart University, 17100 Canakkale, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1595-585X","authenticated-orcid":false,"given":"Nurcan","family":"Berber","sequence":"additional","affiliation":[{"name":"Vocational School of Health Services, \u00c7anakkale Onsekiz Mart University, 17100 Canakkale, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Aminov, R.I. 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