Title : Natural radiomodulation by opuntia ficus-indica cladode extract: Protection against oxidative and clustered DNA damage while enhancing radiosensitivity

The combination of chemotherapy and ionizing radiation is widely used in cancer treatment but frequently causes extensive DNA damage in normal tissues, thereby limiting therapeutic efficacy and increasing treatment-related toxicity. Natural radiomodulators have emerged as promising adjuvants capable of improving treatment selectivity. Among these, Opuntia ficus-indica cladode extract (CCE), a rich source of antioxidant phytochemicals, has attracted increasing attention; however, its effects under combined chemoradiotherapy conditions remain largely unexplored.

Here, we investigated the radiomodulatory potential of CCE against cisplatin- and γ-radiation-induced DNA damage and evaluated its radiosensitizing activity in a microbial model. Plasmid DNA (pGEM-3Zf−) was incubated with cisplatin and exposed to γ-radiation in the presence or absence of CCE. DNA damage was quantified by agarose gel electrophoresis together with lesion-specific enzymatic assays detecting oxidized purine and pyrimidine lesions. Radiosensitization was assessed by determining bacterial D?? values following irradiation.

CCE markedly reduced radiation- and cisplatin-induced genotoxicity, decreasing double-strand break formation by 55% and suppressing the conversion of oxidative base lesions into strand breaks by up to 69%. Moreover, clustered DNA damage was reduced by more than 60%, demonstrating effective protection against complex oxidative lesions. In contrast, CCE significantly enhanced bacterial radiosensitivity in a dose-dependent manner, reducing the D?? value from 2.0 kGy to 0.625 kGy.

These findings reveal a previously unrecognized dual radiomodulatory activity of CCE, combining radioprotection of DNA with radiosensitization in microbial systems. This dual functionality suggests that Opuntia ficus-indica cladode extract may serve as a promising natural adjuvant for chemoradiotherapy by protecting normal tissues from treatment-induced genotoxicity while enhancing radiation efficacy against biological targets.

Saloua Kouass Sahbani is an Assistant Professor at the College of Applied Medical Sciences, Taibah University, Saudi Arabia. She holds PhDs in Radiation Sciences and Biomedical Imaging from the University of Sherbrooke and in Biochemistry and Molecular Biology from Carthage University. Her research focuses on radiation-induced DNA damage, radiosensitization, and radioprotection, with aparticular interest in natural compounds.