PARENT SESSION

Cell and Tissue Signaling

(PP224) Comparison of initial and long term damage in irradiated and bystander populations.

Kadhim, Munira^*,1, Kelly, James¹, Moor, Stephen¹, Smyth, Sharon¹, Goodwin, Edwin², ¹ Radiation & Genome Stability Unit, Harwell, Oxfordshire, UK² Biosciences Division, Los Alamos, New Mexico, USA

ABSTRACT- Genomic instability describes an increased rate in the accumulation of new genetic alterations and is a hallmark of tumorigenesis. It is observed in a fraction of the progeny of cells surviving direct radiation exposure and also in those that were never irradiated but communicated with irradiated cells (bystander cells). Currently, the underlying mechanism for the induction and perpetuation of genomic instability is poorly understood. The purpose of this study is to understand the relationship between the initiating lesion leading to early damage induction and the long term effects in irradiated and bystander cells. Primary human fibroblasts were plated using a novel co-culture system allowing communication between irradiated and bystander populations via medium-borne factors. Irradiated cells were exposed to 0.5 Gy alpha particles and communicated with bystander cells for 0min, 30min, 90min and 24 hours before -H2AX and comet analysis. Populations were then cultured separately for several population doublings and reassessed using -H2AX immunostaining, comet assay and cytogenetics. The number of -H2AX foci increased in irradiated cells up to 90 minutes post-irradiation, with no comparable increase in the bystander population. The comet assay revealed increased damage in irradiated cells at 30 minutes post-treatment, with a similar trend observed at passage 10, suggesting that the initial response determines the level of delayed damage. Chromosomal analysis is currently ongoing and will be discussed. Genomic instability has been observed in both irradiated and bystander cells under environmentally relevant exposure conditions. As such, both are extremely relevant for the extrapolation of radiation exposure dosimetry and potential cancer risk associated with exposure to ionising radiation.

Key words: genomic instability, bystander effect