OC-123 Obesity drives radioresistance and enhances genomic instability in oesophageal adenocarcinoma

IntroductionObesity is strongly associated with oesophageal adenocarcinoma (OAC). However, its role in regulating radiosensitivity and genomic instability is unknown. We developed an isogenic model of radioresistance in OAC called OE33R. We assessed levels of anaphase bridges, a functional genomic instability event, in OE33R compared to an age and passage matched control (OE33P). Spindle assembly checkpoint (SAC) control genes involved in regulating genomic instability were analysed in both cell lines following exposure to adipose conditioned media (ACM). Radiosensitivity following ACM treatment was investigated in OE33R and OE33P cell lines. The aim of this study was to characterise the isogenic radioresistant OAC cell model in terms of genomic instability, SAC gene expression and survival in response to adipose conditioned media (ACM) cultured from obese and nonobese OAC patients.MethodsOE33R and OE33P cell lines were cultured with ACM from obese and nonobese patients. We assessed anaphase bridges in both lines and quantified the number of bridges present over the total cell number. Expression of five SAC genes (MAD2L2, BUB1B, CDC20, CENPE, and ESPL1) was assessed using qPCR. Survival was determined in both cells lines following ACM treatment using a clonogenic assay.ResultsOE33P and OE33P showed a significant increase in anaphase bridges in response to ACM (p