Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation

Abstract

Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signalling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 nu mice after irradiating their brains using pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble France. Athymic nude mice injected with F98 glioma cells into their right cerebral hemisphere 7 days earlier were treated with either MRT or PB.After recovery times of 2, 12 and 48h, the urinary bladders were extracted and cultured as tissue explants for 24h. The growth medium containing the potential signalling factors was harvested, filtered and transferred to HaCaT reporter cells to assess their clonogenic survival and calcium signalling potential. The results show that in the tumour free-mice both treatment modalities produce strong bystander/abscopal signals using the clonogenic reporter assay, however the calcium data do not support a calcium channel mediated mechanism.The presence of tumour reduces or reverses the effect. PB produced significantly stronger effects in the bladders of tumour bearing animals. We conclude that immunocompromised mice produce signals, which can alter the response of unirradiated reporter cells, however a novel mechanism appears to be involved.

Microbeam radiation therapy — grid therapy and beyond: a clinical perspective

“…A series of studies reporting bystander and abscopal effects was published after collaborative work between the group of Elisabeth Schültke and the radiobiology laboratory of Carmel Mothersill. 34 – 38 Bystander effects were also reported by another research group. 39 …”

Animal Models in Microbeam Radiation Therapy: A Scoping Review

“…In a model of 9LGS cells implanted in nude mice (strain not reported), a significant increase of tumoral apparent diffusion coefficient (ADC), consistent with an increase of vascular permeability, was shown 24 h after the delivery of two orthogonally cross-planar MRT arrays (25 µm; 211 ctc; 500 Gy peak-dose) in irradiated tumours versus unirradiated controls [46]. In addition, athymic nude mice (Crl:NU-Foxn1nu) were implanted with F98 glioma cells to establish that bystander and abscopal effects can also be detected in athymic mice after MRT irradiation (50 µm; 200 ctc; 22 or 110 Gy peak-dose) [47].…”

“…When it comes to the effects on non-irradiated tissues (outside of the microbeam array), responses such as genotoxic effects [77] and clonogenic cell death on cells exposed to signals from the irradiated animal [19,43] have been observed after MRT. Some of those responses have involved the immune system [47], with some author suggesting that a functional immune system is key to observe such genotoxic effects post MRT [86].…”

Biological Entanglement–Like Effect After Communication of Fish Prior to X-Ray Exposure

“…All suggest that allowing 2 populations of fish to meet for the first time, then separate never to meet again, before 1 group in each experiment is irradiated, leads to effects in the nonirradiated bystander fish. We have previously published extensively that postirradiation meeting causes effects in nonirradiated fish, rats, and mice, 50 , 51 , 66 , 67 and other groups also have shown these organism level effects in frogs, mice, and water fleas, 68 – 70 but this is the first report of preirradiation meeting, influencing outcome. At first sight, the results may seem beyond strange but the robust and well-tested assays require some consideration and explanation.…”