Heavy ion irradiation induces autophagy in irradiated C2C12 myoblasts and their bystander cells

Hino, Mizuki*; Hamada, Nobuyuki*; Tajika, Yuki*; Funayama, Tomoo; Morimura, Yoshihiro*; Sakashita, Tetsuya; Yokota, Yuichiro; Fukamoto, Kana*; Muto, Yasuko; Kobayashi, Yasuhiko; Yorifuji, Hiroshi*

Autophagy is one of the major processes involved in the degradation of intracellular materials. Here, we examined the potential impact of heavy ion irradiation on the induction of autophagy in irradiated C2C12 mouse myoblasts and their non-targeted bystander cells. In irradiated cells, ultrastructural analysis revealed the accumulation of autophagic structures at various stages of autophagy (i.e. phagophores, autophagosomes and autolysosomes) within 20 min after irradiation. Multivesicular bodies (MVBs) and autolysosomes containing MVBs (amphisomes) were also observed. Heavy ion irradiation increased the staining of microtubule-associated protein 1 light chain 3 and LysoTracker Red (LTR). Such enhanced staining was suppressed by an autophagy inhibitor 3-methyladenine. In addition to irradiated cells, bystander cells were also positive with LTR staining. Altogether, these results suggest that heavy ion irradiation induces autophagy not only in irradiated myoblasts but also in their bystander cells.