The Effect of Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates

Overview

Journal J Clin Med Res

Specialty General Medicine

Date 2018 Oct 23

PMID 30344816

Citations 3

Authors

Shin-Ichiro Masunaga

Junya Kobayashi

Keizo Tano

Yu Sanada

Minoru Suzuki

Koji Ono

Affiliations

Soon will be listed here.

Abstract

Background: The aim of the study was to clarify the effect of status of tumor cells on radio-sensitivity of solid tumors following γ-ray irradiation at various dose rates, referring to the response of intratumor quiescent (Q) cells.

Methods: Human head and neck squamous cell carcinoma cells transfected with mutant (SAS/) or with neo vector (SAS/) were injected subcutaneously into hind legs of nude mice. Tumor bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays at a high, middle or low dose rate. Immediately or 9 h after the high dose-rate irradiation (HDR, 2.5 Gy/min), or immediately after the middle (MDR, 0.039 Gy/min) or low (LDR, 0.00098 Gy/min) dose-rate irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU.

Results: Following γ-ray irradiation, SAS/ tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/ tumors that showed little repair capacity. The recovery capacities following γ-ray irradiation were greater in Q than total cell population and increased in the following order of 9 h after HDR < MDR < LDR. Thus, the difference in radio-sensitivity between the total (P + Q) and Q cells after γ-ray irradiation increased in the same order.

Conclusion: To secure controlling solid tumors as a whole, difference in sensitivity between total and Q tumor cells especially in solid tumors irrespective of status has to be suppressed as irradiation dose rate decreases, for instance, through employing combined method for enhancing the response of Q tumor cells.

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References

Karran P . DNA double strand break repair in mammalian cells. Curr Opin Genet Dev. 2000; 10(2):144-50. DOI: 10.1016/s0959-437x(00)00069-1. View

Wulf J, Haedinger U, Oppitz U, Thiele W, Mueller G, Flentje M . Stereotactic radiotherapy for primary lung cancer and pulmonary metastases: a noninvasive treatment approach in medically inoperable patients. Int J Radiat Oncol Biol Phys. 2004; 60(1):186-96. DOI: 10.1016/j.ijrobp.2004.02.060. View

Coleman M, Yin E, Peterson L, Nelson D, Sorensen K, Tucker J . Low-dose irradiation alters the transcript profiles of human lymphoblastoid cells including genes associated with cytogenetic radioadaptive response. Radiat Res. 2005; 164(4 Pt 1):369-82. DOI: 10.1667/rr3356.1. View

Sigal A, Rotter V . Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. Cancer Res. 2001; 60(24):6788-93. View

Ohnishi K, Wang X, Takahashi A, Ohnishi T . Contribution of protein kinase C to p53-dependent WAF1 induction pathway after heat treatment in human glioblastoma cell lines. Exp Cell Res. 1998; 238(2):399-406. DOI: 10.1006/excr.1997.3842. View

Schwartz J, Rasey J, Wiens L, Jordan R, Russell K . Functional inactivation of p53 by HPV-E6 transformation is associated with a reduced expression of radiation-induced potentially lethal damage. Int J Radiat Biol. 1999; 75(3):285-91. DOI: 10.1080/095530099140465. View

Todd P, Wood J, Walker J, Weiss S . Lethal, potentially lethal, and nonlethal damage induction by heavy ions in cultured human cells. Radiat Res Suppl. 1985; 8:S5-12. View

Hammond E, Dorie M, Giaccia A . ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in response to reoxygenation. J Biol Chem. 2003; 278(14):12207-13. DOI: 10.1074/jbc.M212360200. View

Wu H, Hada M, Meador J, Hu X, Rusek A, Cucinotta F . Induction of micronuclei in human fibroblasts across the Bragg curve of energetic heavy ions. Radiat Res. 2006; 166(4):583-9. DOI: 10.1667/RR0535.1. View

10.

Horn H, Vousden K . Coping with stress: multiple ways to activate p53. Oncogene. 2007; 26(9):1306-16. DOI: 10.1038/sj.onc.1210263. View

11.

Masunaga S, Ono K, Abe M . Potentially lethal damage repair by quiescent cells in murine solid tumors. Int J Radiat Oncol Biol Phys. 1992; 22(5):973-8. DOI: 10.1016/0360-3016(92)90796-k. View

12.

Vaupel P, Kelleher D . Pathophysiological and vascular characteristics of tumours and their importance for hyperthermia: heterogeneity is the key issue. Int J Hyperthermia. 2010; 26(3):211-23. DOI: 10.3109/02656731003596259. View

13.

Sannigrahi M, Singh V, Sharma R, Panda N, Khullar M . Role of autophagy in head and neck cancer and therapeutic resistance. Oral Dis. 2014; 21(3):283-91. DOI: 10.1111/odi.12254. View

14.

Tsuruoka C, Blyth B, Morioka T, Kaminishi M, Shinagawa M, Shimada Y . Sensitive Detection of Radiation-Induced Medulloblastomas after Acute or Protracted Gamma-Ray Exposures in Ptch1 Heterozygous Mice Using a Radiation-Specific Molecular Signature. Radiat Res. 2016; 186(4):407-414. DOI: 10.1667/RR14499.1. View

15.

Masunaga S, Ono K, Takahashi A, Ohnishi T, Kinashi Y, Takagaki M . Radiobiological characteristics of solid tumours depending on the p53 status of the tumour cells, with emphasis on the response of intratumour quiescent cells. Eur J Cancer. 2002; 38(5):718-27. DOI: 10.1016/s0959-8049(01)00430-0. View

16.

Sumiyoshi K, Strebel F, Rowe R, Bull J . The effect of whole-body hyperthermia combined with 'metronomic' chemotherapy on rat mammary adenocarcinoma metastases. Int J Hyperthermia. 2003; 19(2):103-18. DOI: 10.1080/0265673021000017091. View

17.

Ota I, Ohnishi K, Takahashi A, Yane K, Kanata H, Miyahara H . Transfection with mutant p53 gene inhibits heat-induced apoptosis in a head and neck cell line of human squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2000; 47(2):495-501. DOI: 10.1016/s0360-3016(00)00437-5. View

18.

Bindra R, Schaffer P, Meng A, Woo J, Maseide K, Roth M . Alterations in DNA repair gene expression under hypoxia: elucidating the mechanisms of hypoxia-induced genetic instability. Ann N Y Acad Sci. 2005; 1059:184-95. DOI: 10.1196/annals.1339.049. View

19.

Kato F, Ootsuyama A, Nomoto S, Kondo S, Norimura T . Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis. Int J Radiat Biol. 2001; 77(1):13-9. DOI: 10.1080/09553000010001899. View

20.

Masunaga S, Nagata K, Suzuki M, Kashino G, Kinashi Y, Ono K . Inhibition of repair of radiation-induced damage by mild temperature hyperthermia, referring to the effect on quiescent cell populations. Radiat Med. 2007; 25(8):417-25. DOI: 10.1007/s11604-007-0160-4. View