First in vitro cell co-culture experiments using laser-induced high-energy electrons FLASH irradiation for the development of anti-cancer therapeutic strategie

By Nicholas Yeboah, Resa Nelson, and Adam Nahor

Researchers were able to administer ultrahigh dose rates (UHDRs) to melanoma cells (skin cancer) in an in vitro cell co-culture experiment with healthy melanocytes. They were able to target the cancer cells and minimize DNA damage in healthy melanocytes while simultaneously increasing the potency of the radiation.

Radiotherapeutic treatments have been developed to combat solid cancers (tumors); however, issues present with these treatments include damage to healthy cells surrounding cancerous ones. This study compared conventional X-ray irradiation methods to the newer, ultrahigh dose rate (UHDR) irradiation, known as FLASH. With dose rates higher than 40 Gy/s, radiotherapy can be delivered quickly, minimizing damage to the surrounding, healthy cells, creating the “FLASH” effect. The findings are paramount, because UHDR-induced FLASH effect has only been tested in in-vivo models, never in-vitro. In-vitro testing will allow us to fully understand the effectiveness of UHDRs and demonstrate its potential to combat tumors while limiting the side effects.

Orobeti et al assembled a high intensity laser apparatus to treat a co-culture of melanocytes and melanomas to compare to their conventional pulsed x-ray irradiation apparatus. Cell co-cultures containing both the melanocytes and melanomas were placed in the paths of the irradiation sources and results (intensity of irradiation exposure and double stranded DNA breaks) were measured. The researchers focused on counting the number of foci (indicating double-stranded DNA breakages) using immunofluorescence analysis/microscopy and TissueQuest, a segmentation analysis software, to determine the effectiveness of each treatment. 

Frequency distributions of the number of foci per cell for each treatment group shows  that UHDR treatment caused more DNA damage to cancer cells when compared to normal cells. This could be due to the fact that normal cells are better at repairing DNA damage than cancerous cells; therefore, the DNA damage dealt on normal cells is far less impacting than the cancerous melanocytes. Nevertheless, the results of this study show that in-vitro testing with UHDRs can be done. It also shows the efficiency and potential of UHDRs to replace conventional solid cancer treatments such as pulsed x-rays irradiation. 

Further studies could be done to look at the dosage effects of UHDRs in tumor cells. Doing so will allow us to fully understand the dosage threshold that could be applied for maximum effectiveness while minimizing damage to surrounding, healthy cells.

Citations

Orobeti, S., Sima, L.E., Porosnicu, I. et al. First in vitro cell co-culture experiments using laser-induced high-energy electron FLASH irradiation for the development of anti-cancer therapeutic strategies. Sci Rep 14, 14866 (2024). https://doi.org/10.1038/s41598-024-65137-7

Repairing DNA Damage in Cancer Cells | Memorial Sloan Kettering Cancer Center. (2021, January 11). https://www.mskcc.org/news/repairing-dna-damage-cancer-cells