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Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy

1
Department of Radiation Oncology, Gunma Prefectural Cancer Center, Gunma 373-8550, Japan
2
Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan
3
QST Hospital, National Institute for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
4
Gunma University Initiative for Advanced Research (GIAR), Gunma University, Gunma 371-8511, Japan
5
Gunma University Heavy Ion Medical Center, Gunma 371-8511, Japan
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2020, 10(3), 110; https://doi.org/10.3390/jpm10030110
Received: 11 August 2020 / Revised: 28 August 2020 / Accepted: 1 September 2020 / Published: 3 September 2020
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy specimens were obtained from seven prospectively recruited patients with cervical cancer, before treatment and after receiving radiotherapy at a dose of 10 Gy (in five fractions). The samples were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, and 200 nuclei per sample were randomly identified and assessed for the presence of MN or apoptosis, based on nuclear morphology. The median number of MN-harboring nuclei was significantly greater in samples from patients treated with radiotherapy than in pre-treatment samples (151 (range, 16–327) versus 28 (range, 0–61); p = 0.015). No significant differences in the number of apoptotic nuclei were observed between pre-treatment and 10 Gy samples (5 (range, 0–30) versus 12 (range, 2–30); p = 0.30). This is the first report to demonstrate MN induction by radiotherapy in solid tumors. The results provide clinical evidence of the activation of antitumor immune responses by radiotherapy. View Full-Text
Keywords: micronuclei; uterine cervical cancer; radiotherapy; cGAS; STING; abscopal effect; immunotherapy micronuclei; uterine cervical cancer; radiotherapy; cGAS; STING; abscopal effect; immunotherapy
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MDPI and ACS Style

Kobayashi, D.; Oike, T.; Murata, K.; Irie, D.; Hirota, Y.; Sato, H.; Shibata, A.; Ohno, T. Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy. J. Pers. Med. 2020, 10, 110. https://doi.org/10.3390/jpm10030110

AMA Style

Kobayashi D, Oike T, Murata K, Irie D, Hirota Y, Sato H, Shibata A, Ohno T. Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy. Journal of Personalized Medicine. 2020; 10(3):110. https://doi.org/10.3390/jpm10030110

Chicago/Turabian Style

Kobayashi, Daijiro; Oike, Takahiro; Murata, Kazutoshi; Irie, Daisuke; Hirota, Yuka; Sato, Hiro; Shibata, Atsushi; Ohno, Tatsuya. 2020. "Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy" J. Pers. Med. 10, no. 3: 110. https://doi.org/10.3390/jpm10030110

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