Genotoxic and mutagenic potential of non-thermal plasma: Mechanistic insights from eukaryotic cell studies

Non-thermal plasma (NTP), a partially ionized gas enriched with reactive oxygen and nitrogen species (RONS) and UV radiation, is increasingly used in medicine, agriculture, and food processing applications. While its oxidative and antimicrobial effects are well documented, the molecular mechanisms underlying its genotoxic and mutagenic effects in eukaryotic systems remain poorly understood. This review consolidates the current evidence on how NTP interacts with cellular and molecular targets to induce DNA damage. Key mechanisms are identified that link plasma-generated RONS and physical components to base oxidation (8-oxoG formation), single- and double-strand breaks (γ-H2AX foci), and chromosomal instability (micronuclei formation). The extent and nature of these effects are further influenced by plasma parameters-including source configuration, working gas composition, exposure duration, and delivered dose-as well as by intrinsic cellular factors such as DNA repair capacity, antioxidant defenses, and overall metabolic state. In addition to cataloguing genotoxic outcomes, this review synthesizes mechanistic insights across unicellular, plant, and animal models, emphasizing comparative sensitivity, methodological variability, and the influence of plasma dosimetry on biological responses. By integrating these findings, we highlight both the potential therapeutic selectivity of NTP-particularly against tumor cells-and the remaining challenges for safe biomedical translation.