The influence of smoking on radiation-induced bystander signal production in esophageal cancer patients

- A fast and non-invasive blood based assay has been developed to assess the production of radiation induced bystander signals in humans.
- Two known environmental carcinogens (radiation & smoking) are shown to interact in this cohort of cancer patients.
- Samples taken from smokers do not produce bystander signals, whereas samples taken from non-smokers can.
- This has implications for radiation protection where at present radiation risk is assessed independently of other risks such as smoking status.
- It is likely that these effects hold for humans in general.

The relevance of radiation-induced bystander effects in humans is unclear. Much of the existing data relate to cell lines but the effect of bystander signals in complex human tissues is unclear. A phase II clinical study was untaken, where blood sera from 60 patients along with 15 cancer-free volunteers were used to detect whether measurable bystander factor(s) could be found in the blood following high dose rate (HDR) brachytherapy. Overall, there was no significant change in bystander signal production (measured in a human keratinocyte reporter system) before and after one treatment fraction of HDR brachytherapy (p>0.05). Further assessment of patient characteristics and environmental modifiable factors including smoking were also analyzed. Similar to previously published data, samples taken from smokers produced weaker signals compared to non-smokers (p<0.05). Although the number of non-smoking subjects was low, there was a clear decrease in cloning efficiency observed in keratinocyte cultures for these patients that requires further study. This study found that samples taken from smokers do not produce bystander signals, whereas samples taken from non-smokers can produce such signals following HDR brachytherapy. These findings highlight the importance of studying the interactions of multiple stressors including environmental modifiers with radiation, since some factors such as smoking may elicit protection in tumor cells which could counteract the effectiveness of radiation therapy.