Differential cell death pathways in normal and cancerous breast cells response to direct X-ray irradiation and bystander effects

Abstract

This study investigates distinct cell death pathways in directly irradiated and non-irradiated bystander cells using MCF-7 breast cancer and MCF-10A normal breast cells. Both cell types were exposed to 6 MV X-ray radiation (0–5 Gy). Non-radiated bystander cells were co-cultured with irradiated cells using a transwell system to assess radiation-induced bystander effects. Cell survival was measured by clonogenic assays, and apoptosis, mitotic catastrophe, and senescence were evaluated morphologically. The results showed that bystander and directly irradiated MCF-7 and MCF-10A cells exhibited reduced survival, with a more pronounced effect in irradiated cells. Apoptosis was the dominant cell death pathway in both conditions, with MCF-7 bystander cells exhibiting an earlier onset than MCF-10A cells. Apoptosis rates exceeded 23% at doses above 4 Gy. Mitotic catastrophe was more common at higher doses, with MCF-7 bystander cells responding at 4 Gy and MCF-10A irradiated cells at 4.5 Gy. Senescence was primarily observed in bystander cells, with higher levels in MCF-7 and MCF-10A bystander cells compared to irradiated cells. These findings indicate that while apoptosis and mitotic death are prevalent in directly irradiated cells, bystander cells predominantly experience apoptosis and senescence. The differential responses between cancerous and normal cells highlight the potential for optimizing radiation therapy to target cancer cells more effectively while preserving healthy tissue.