First in vitro cell co-culture experiments using laser-induced high energy electron FLASH irradiation – potential for anti-cancer therapeutic strategies

Abstract

Abstract Radiation delivery at ultra-high dose rates (UHDRs) demonstrated its potential to be used as a new anti-cancer therapeutic strategy. The FLASH effect induced by UHDR irradiation was shown to maintain anti-tumor efficacy while reducing normal tissue toxicity that limits the use of conventional radiotherapy, however, the FLASH effect was difficult to demonstrate in vitro. The new high-intensity petawatt laser-driven accelerators can deliver very high energy electrons (VHEE) at dose rates as high as 1013 Gy/s in very short pulses (10− 13 s). We present here the first in vitro experiments carried out on cancer cells and normal non-transformed cells exposed concurrently to laser-plasma accelerated (LPA) electrons. Specifically, melanoma cancer cells and normal melanocyte co-cultures grown in chamber slides were simultaneously irradiated by LPA electrons. Non-uniform dose distribution on cell cultures was revealed by gafchromic films placed behind the chamber slide supporting the cells. In parallel experiments, cell co-cultures were exposed to pulsed X-ray irradiation, serving as positive controls for radiation-induced nuclear DNA double-strand breaks. By measuring the impact on discrete areas of the cell monolayers, it was revealed that the highest propensity of damaged DNA-containing nuclei was achieved by LPA electrons at a cumulated dose of one order of magnitude lower than the dose obtained by pulsed X-ray irradiation. Interestingly, on certain discrete areas, we observed that LPA electron exposure had a different pattern of DNA damage impact on healthy NHEM melanocyte cells than on the A375 melanoma cells – normal cells were less affected than cancer cells.