Differential Radiomodulatory Effects of Sodium Aminodihydrophthalazinedione (Tameron^®) on Normal and Cancer Cells...

Radiotherapy is one of the most effective methods of cancer treatment. New, more effective, and safer radiotherapy methods can be developed thanks to selective radioprotectors. In our study, we investigated the antioxidant and radiomodulatory activity of sodium aminodihydrophthalazinedione (the drug Tameron^®) on human mesenchymal stem cells (MSCs) and human osteosarcoma cells of the MNNG/Hos line in vitro. We have shown that sodium aminodihydrophthalazinedione effectively scavenged radiation-induced hydrogen peroxide in aqueous solution in a concentration-dependent manner after X-ray irradiation. We also showed that sodium aminodihydrophthalazinedione (0.25 mM and above) effectively protects human MSCs from the damaging effects of X-rays, reducing the level of intracellular ROS and the number of apoptotic cells after irradiation, enhancing the restoration of double-stranded DNA breaks and clonogenic activity. Meanwhile, the effect of sodium aminodihydrophthalazinedione on human osteosarcoma MNNG/Hos cells was different: it increased the number of apoptotic cells and reduced the rate of repair of double-stranded DNA breaks. Transcriptomic studies on both cell culture types using nanopore sequencing technology after X-ray irradiation and sodium aminodihydrophthalazinedione pretreatment revealed a significant level of modulation of key genes responsible for DNA repair, antioxidant activity, and genome stability. Our data show that sodium aminodihydrophthalazinedione may be a promising therapeutic agent for modulating the cellular effects of radiation exposure.