Aspirin protects against genotoxicity by promoting genome repair

Abstract

Dear Editor,Radiation sickness is a major health concern. 1 The quest for radiation countermeasures started in the wake of the devastation witnessed following the nuclear detonations during the Second World War and has continued through the subsequent radiological accidents around the world. A radioprotector is also required for prophylactic use by staff working at radiation sources, pilots, and astronauts at high risk of space radiation, or patients undertaking lengthy radiological procedures. Despite decades of research, a safe, efficient, and cost-effective radioprotector is yet to be unveiled.Acetylsalicylic acid (aspirin) is the oldest drug in the history of medicine. It has been used for over 4000 years for the treatment of pain, inflammation, fever, and more recently for cardiovascular prophylaxis 2 and cancer prevention. 3 Bone marrow failure is the primary cause of mortality following irradiation. Hence, protecting the bone marrow is a primary goal in the development of radiation countermeasures. Inflammation is a key outcome and driver of irradiation-induced tissue injury. 4 Given its anti-inflammatory effects, we inquired whether aspirin could protect against radiation. When inoculated into mice, aspirin protected against irradiation-induced bone marrow ablation (Fig. 1a; Supplementary information, Fig. S1a-d) and suppressed the induction of inflammatory genes including Ifnb1, Mx1 and Tnfa in vivo and in bone marrow-derived monocytes (BMDMos) (Supplementary information, Figs. S1e-g and S2a-c).

Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence

“…As for WT mice, the apoV group showed higher survival rates (30‐day survival rate: 5/7) than the PBS group (30‐day survival rate: 2/7), along with prolonged survival time (Figure 4a), reduced weight loss (Figure 4b), decreased numbers of γH2AX foci in multiple organs (Figure 4c‐g) and improved 24‐h survival of bone marrow cells compared to the PBS group (Figure 4h). Among the tissues we examined, the bone marrow was the most severely damaged after irradiation (Jiang et al., 2023; Mettler & Voelz, 2002). We harvested bone marrow cells from a femur and tibia, lysed the red blood cells, and counted the total number of cells as previously described (Zhao et al., 2014).…”

“…Nuclear radiation poses a significant challenge to future society (Mettler & Voelz, 2002). However, to date, more attention has been given to drugs that inhibit DNA repair, and there has been limited research on effective DNA repair medications (Jiang et al., 2023). Although it has been suggested that some agents, such as aspirin, exhibit anti‐inflammatory and DNA repair effects in irradiation‐induced damage, clinically there is no effective therapeutic approach to treating irradiation‐induced DNA damage (Jiang et al., 2023).…”

“…However, to date, more attention has been given to drugs that inhibit DNA repair, and there has been limited research on effective DNA repair medications (Jiang et al., 2023). Although it has been suggested that some agents, such as aspirin, exhibit anti‐inflammatory and DNA repair effects in irradiation‐induced damage, clinically there is no effective therapeutic approach to treating irradiation‐induced DNA damage (Jiang et al., 2023). However, as an emerging biological therapeutic approach, the therapeutic potential of EVs, particularly apoVs, for radiation damage treatment is still unknown.…”

“…After the experimental treatment, mBMMSCs were harvested by briefly centrifuging and resuspended into cold PBS at a concentration of approximately 10 6 cells/ml. The comet assay was performed as described previously (Jiang et al., 2023). The detailed experimental procedures and the reagents employed are provided in supplementary materials.…”

The PIG‐A gene mutation assay in human biomonitoring and disease

“…In addition, aspirin intake may be protective against an increase in PIG-A mutation levels. Whilst the anti-cancer effects of aspirin have been well-documented (Jiang et al, 2023), the specific interaction of dietary intake and erythrocyte mutant levels remains unclear. Cancer treatment, that is, chemo or radiotherapy, may also change mutation levels.…”