Ionizing radiation is widely used in medicine but can cause genotoxic and cytotoxic effects in healthy tissues. Natural radioprotectors represent a promising strategy to mitigate the radiation-induced damage. This study investigates the radioprotective efficacy of a mucilage extract from Opuntia ficus-indica (OFI) cladodes in human peripheral blood lymphocytes (PBLs). PBLs were treated with two concentrations of OFI extract (0.01 and 0.05 µg/mL) and assessed for cytotoxicity, viability and chromosomal integrity. Cytokinesis block micronucleus (CBMN) assay and cytokinesis block proliferation index (CBPI) were used to evaluate genotoxicity and cytotoxicity, respectively. For radioprotection assays, PBLs were pretreated with OFI extract prior to exposure to ⁶⁰Co γ-rays (0.5 and 1 Gy) and the frequency of micronuclei was determined. OFI extract per se did not induce cytotoxic or genotoxic effects. Exposure to gamma radiation significantly increased micronuclei frequency in a dose-dependent manner. Pretreatment with OFI extract resulted in a significant reduction in radiation-induced micronuclei formation at 1 Gy total absorbed dose, indicating a protective effect against chromosome damage. In conclusion, OFI mucilage extract is non-toxic to human lymphocytes and exhibits radioprotective potential, likely due to its bioactive phytocompounds. These preliminary findings support further investigation of OFI as a natural radioprotective agent in clinical or environmental settings. © The Author(s) 2025.

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