Radiation induces ferroptosis in the presence of AA. (A–C) Percentage of dead FHs74Int cells, treated with indicated PUFAs (20 or 40 μM) or/and Fer-1 (5 μM), detected at 120 h after irradiation. αLA: α-Linolenic acid; LA: Linoleic acid; DHA: Docosahexaenoic acid; AA: Arachidonic acid. (D) Lipid peroxidation levels in FHs74Int cells, in the absence or presence of AA (40 μM) and Fer-1 (5 μM), detected at 72 h after 10 Gy irradiation. (E) Percentage of dead FHs74Int cells, treated with AA (40 μM) or/and RSL3 (0.05 μM), detected at 120 h after 10 Gy irradiation. (F) Lipid peroxidation levels in FHs74Int cells, in the absence or presence of AA (40 μM) and RSL3 (0.05 μM), detected at 72 h after 10 Gy irradiation. (G) Representative images of intestinal crypt organoids in indicated groups captured at D9 post IR in the presence or absence of AA (100 μM). Organoids were pretreated with Fer-1 (10 μM) or/and AA for 24 h followed by 6 Gy irradiation, and the culture medium was replaced every 24 h. Scale bar: 50 μm. Quantification of survived organoids are depicted in (H). (I) Schema of AA gavage and irradiation treatment. (J) AA levels in jejunums from Ctrl and AA gavage mice measured by ELISA at D4 (n = 3). (K) The percent survival of mice after 15 Gy ABI in the presence or absence of AA. *: p < 0.05, **: p < 0.01, ***: p < 0.001, NS: no significance.