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. 2020 Oct 24;20(1):390.
doi: 10.1186/s12883-020-01966-z.

Ex vivo radiosensitivity is increased in non-cancer patients taking valproate

Jenny Stritzelberger  1 , Jennifer Lainer  2 , Stefanie Gollwitzer  3 , Wolfgang Graf  3 , Tina Jost  2 , Johannes D Lang  3 , Tamara M Mueller  3 , Stefan Schwab  3 , Rainer Fietkau  2 , Hajo M Hamer  3 , Luitpold Distel  2
Affiliations

Ex vivo radiosensitivity is increased in non-cancer patients taking valproate

Jenny Stritzelberger et al. BMC Neurol. .

Abstract

Background: Valproate (VPA) is a commonly prescribed antiepileptic drug for patients experiencing epileptic seizures due to brain tumors. VPA increases radiation sensitivity in various tumor cells in vitro due to complex mechanisms. This could make tumors more vulnerable to ionizing radiation or overcome radioresistance. Yet, clinical data on possible improvement of tumor control by adding VPA to tumor therapy is controversial. Potentially radiosensitizing effects of VPA on healthy tissue remain unclear. To determine individual radiosensitivity, we analyzed blood samples of individuals taking VPA.

Methods: Ex vivo irradiated blood samples of 31 adult individuals with epilepsy were studied using 3-color fluorescence in situ hybridization. Aberrations in chromosomes 1, 2 and 4 were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M) and compared to age-matched (2:1) healthy donors.

Results: The patient cohort (n = 31; female: 38.7%) showed an increase of their average B/M value compared to healthy individuals (n = 61; female: 56.9%; B/M: 0.480 ± 0.09 vs. 0.415 ± 0.07; p = .001). The portion of radiosensitive (B/M > 0.500) and distinctly radiosensitive individuals (B/M > 0.600) was increased in the VPA group (54.9% vs. 11.3 and 9.7% vs. 0.0%; p < .001). In 3/31 patients, radiosensitivity was determined prior to and after VPA treatment and radiosensitivity was increased by VPA-treatment.

Conclusions: In our study, we confirmed that patients treated with VPA had an increased radiosensitivity compared to the control group. This could be considered in patients taking VPA prior to the beginning of radiotherapy to avoid toxic side effects of VPA-treatment.

Keywords: 3-colour fluorescence-in-situ-hybridization; Breaks per metaphase; Individual radiosensitivity; Valproate.

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Conflict of interest statement

WG received a lecture fee from UCB and Desitin. HH reports personal fees from UCB, personal fees from Desitin, personal fees from Eisai, personal fees from GW, personal fees from Novartis, personal fees from IQWiG, personal fees from Hexal, personal fees from facetoface, grants from Amgen, Ad-Tech, Bracco, Pfizer, Micromed, Nihon Kohden, personal fees from Arvelle, outside the submitted work. The other authors have nothing to report.

Figures

Fig. 1
Fig. 1
Three-color-FiSH. Three-color fluorescence in situ hybridization to analyze radiosensitivity. Metaphase spreads of human blood lymphocytes, stained with chromosome specific probes for chromosome # 1 (red, rhodamine), chromosome # 2 (green, FITC) and chromosome # 4 (yellow, rhodamine + FITC). DNA was stained with DAPI (blue)
Fig. 2
Fig. 2
Radiosensitivity in patients taking VPA vs. healthy individuals. Number of healthy individuals (blue) and patients (red) classified into divisions of 0.02 breaks per metaphase. B/M background without irradiation a and after irradiation with 2 Gy, corrected by the background b. Radiosensitive patients with a B/M-value at 2 Gy > 0.5 are additionally labelled to show that these patients did not have more spontaneous aberrations (A). The data were fitted by a Gaussian distribution; scale 10 μm
See this image and copyright information in PMC

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