PARENT SESSION

Risks and Modeling at Low Doses

(PP032) Radiation-induced bystander effects in CGL cells for cell killing and neoplastics transformation: implications for radiotherapy.

Blake-James, Molly^*,1, Mill, Andrew¹, Hill, Mark², ¹ Radiation Biophysics Group, Birmingham, West Midlands, England² Radiation and Genome Stability Unit, Harwell, Oxon, England

ABSTRACT-

Radiation-induced bystander effects – when irradiated cells respond as it they have been irradiated either because they are close to exposed cells or because they indirectly receive a signal from them – is an undisputed fact. However, the implications with regard to radiotherapy and radiation risks are still unknown.

Here we describe results using two cell lines (both HeLa x human skin fibroblasts), CGL1 (non-tumourigenic) and   CGL3 (tumourigenic derivation of CGL1) irradiated using ²³⁸Pu –particles (high-LET) and ⁹⁰Sr/Y –particles (low-LET). The end points assessed were survival and neoplastic transformation in vitro. For the –particle irradiations bystander, unirradiated cells were in continuous contact with irradiated cells; for the –particle irradiations bystander effects were investigated by medium transfer from irradiated cells.

Medium transfer from both irradiated CGL1 and CGL3 cells (0.5 – 6 Gy) resulted in reduced survival (by 15 – 20 %) in recipient CGL1 cells, with an independence from dose above 1 Gy.

CGL1 cells exposed to 1 Gy –particles produced a significantly enhanced (i.e. greater than spontaneous level) transformation frequency in neighbouring, unexposed CGL1 cells. The transformation frequency in bystander cells was equivalent to that observed for cells irradiated with ∼0.6 Gy –particles.

This is the first reported example of a bystander effect for neoplastic transformation in vitro.

Further work is in progress at assess: (1) whether irradiated CGL3 cells can induce elevated levels of neoplastic transformation in CGL1 cells following irradiation with high and low-LET radiation; and (2) whether irradiated CGL1 cells can induce cell killing in CGL3 cells. These studies will also include other radiation sources such as mammography X-rays and radiotherapy X-ray beams. The results of these studies will be presented and the implications for radiation risk and radiotherapy in terms of the risks of induction of secondary cancers will be discussed.

Key words: Bystander effect, Neoplastic transformation