Bystander effect and adaptive response in C3H 10T½ cells

Purpose: To address the relationship between the bystander effect and the adaptive response that can compete to impact on the dose-response curve at low doses. Materials and methods: A novel radiation apparatus, where targeted and non-targeted cells were grown in close proximity, was used to investigate these phenomena in C3H 10T½ cells. It was further examined whether a bystander effect or an adaptive response could be induced by a factor(s) present in the supernatants of cells exposed to a high or low dose of X-rays, respectively. Results: When non-hit cells were co-cultured for 24 h with cells irradiated with 5 Gy (alpha)-particles, a significant increase in both cell killing and oncogenic transformation frequency was observed. If these cells were treated with 2 cGy X-rays 5 h before co-culture with irradiated cells, approximately 95% of the bystander effect was cancelled out. A 2.5-fold decrease in the oncogenic transformation frequency was also observed. When cells were cultured in medium donated from cells exposed to 5 Gy X-rays, a significant bystander effect was observed for clonogenic survival. When cells were cultured for 5 h with supernatant from donor cells exposed to 2 cGy and were then irradiated with 4 Gy X-rays, they failed to show an increase in survival compared with cells directly irradiated with 4 Gy. However, a twofold reduction in the oncogenic transformation frequency was seen. Conclusions: An adaptive dose of X-rays cancelled out the majority of the bystander effect produced by (alpha)-particles. For oncogenic transformation, but not cell survival, radioadaption can occur in unirradiated cells via a transmissible factor(s).