The Bystander Effect of Heavy Ions in Confluent Human Fibroblasts

Significant evidence has been presented demonstrating that ionizing radiation induces biological effects in nonirradiated bystander cells having received signals from directly irradiated cells [1]; however, little information exists on the bystander effect of heavy ions. Less irradiated cells should coexist with more nonirradiated counterparts in a population exposed to a lower dose of higher-LET heavy ions, so that an elucidation of the effects arising not merely in irradiated cells but in their bystander cells would be crucial to comprehend the mechanism of action of heavy ions. Here we have investigated heavy ion-induced bystander response in confluent human fibroblast cultures. First, precise microbeams were employed to target 0.0003% of cells [2]. Conventional broadfield irradiation was carried out in parallel to see the effects in irradiated cells [3-6]. Intriguingly, bystander cells manifested a more transient apoptotic response and delayed p53 phosphorylation, compared with irradiated cells [7]. Taken together, nearly three quarters of the genes whose expression changed in bystander cells were downregulated, and most of the genes upregulated in irradiated cells were downregulated in bystander cells [8]. These findings highlight the distinct response of irradiated and bystander cells. Furthermore, interleukin genes were upregulated in irradiated cells whereas its receptor gene was upregulated in bystander cells [8], suggestive of the signal transmission from irradiated to bystander cells. Second, chromosome aberrations were analyzed in cells treated with conditioned medium from X- or heavy ion-irradiated cells. We found the difference in the types of aberrations, but very little in the total aberration yields [9], indicating that bystander responses occur independently of radiation types but are induced through different mechanisms. Collectively, these induced bystander responses could be a defensive mechanism that would avert or minimize further expansion of aberrant cells.10th International Workshop on Radiation Damage to DN