Effects of cell cycle phase on low-dose hyper-radiosensitivity

Short, Susan C; Woodcock, M.; Marples, Brian; Joiner, Michael C.

doi:10.1080/0955300021000045646

Cited by 71 publications

(37 citation statements)

References 15 publications

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“…Cells synchronized in G 2 /M showed a significantly more pronounced HRS than synchronized cells in G 1 or S. 34 The finding of Short et al presents an interesting explanation of the underlying mechanism of chemo-potentiation by LDFRT in this study. In this study, TXT was given prior to LDFRT which is also known to cause G 2 /M arrest.…”

Section: Discussionmentioning

confidence: 48%

Low Dose Fractionated Radiation Potentiates the Effects of Taxotere in Nude Mice Xenografts of Squamous Cell Carcinoma of Head and Neck

Spring¹,

Arnold²,

Shajahan³

et al. 2004

Cell Cycle

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This study evaluated the combined effect of Low Dose Fractionated Radiation (LDFRT) and Taxotere (TXT) therapy on the growth of SCCHN (squamous cell carcinoma of head and neck; SQ-20B, a p53 mutant SCCHN cell line) tumors in a nude mouse model to exploit the increased hyper radiation sensitivity (HRS) phenomenon present in G 2 /M cell cycle phase when induced by low doses of radiation that was demonstrated in in vitro settings. Seventy-eight animals were randomized into one control group and 5 treatment groups (treatments were administered weekly for six weeks). Tumor regression was observed in all the groups, however, tumor regression was not significant in 2 Gy or TXT or 2 Gy plus TXT treated groups when compared to control group. The tumor regression was significant in both the LDFRT group (p < 0.0043) and LDFRT + TXT group (p < 0.0006) when compared to the other groups. A significantly prolonged tumor growth delay was observed in LDFRT group (p < 0.0081). Importantly, in combination of TXT and LDFRT, no tumor regrowth was observed in 12 out of 13 mice since LDFRT + TXT treatment caused a sustained regression of tumors for 9 weeks. Molecular analysis of resected tumor specimens demonstrated that Bax levels were elevated with a concomitant increase in cytochrome c release into the cytosol in treatment Group VI. These findings strongly suggest that LDFRT can be used in combination with TXT to potentiate the effects of drug on tumor regression through an apoptotic mode of death. Furthermore, the G 2 /M cell cycle arrest by TXT appears to be an important component of the enhanced apoptotic effect of TXT + LDFRT combined treatment.

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Section: Discussionmentioning

confidence: 48%

Low Dose Fractionated Radiation Potentiates the Effects of Taxotere in Nude Mice Xenografts of Squamous Cell Carcinoma of Head and Neck

Spring¹,

Arnold²,

Shajahan³

et al. 2004

Cell Cycle

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“…Short and colleagues (33) showed the influence of cellcycle phases on the HRS phenomenon. Cells synchronized in G 2 -M showed a significantly more pronounced HRS than synchronized cells in G 1 or S. These findings present an interesting explanation of the underlying mechanisms of chemopotentiation by LDFRT in the studies from our laboratory using paclitaxel or docetaxel (18,19).…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Fractionated Radiation Potentiates the Effects of Cisplatin Independent of the Hyper-Radiation Sensitivity in Human Lung Cancer Cells

Gupta

Koru‐Sengul

Arnold

et al. 2011

Molecular Cancer Therapeutics

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In this study, the role of hyper-radiation sensitivity (HRS) in potentiating the effects of cisplatin by low-dose fractionated radiation (LDFRT) was evaluated in four human non-small cell lung cancer cell lines. Presence of HRS and cisplatin enhancement ratio (CER) by LDFRT/2 Gy was assessed using colony-forming and apoptotic assays. Cell-cycle disturbances were studied by flow cytometry. Expression of genes involved in apoptosis was assessed using real-time reverse transcriptase PCR arrays. H-157 cells showed a distinct HRS region, followed by UKY-29 and A549 cells, whereas it was absent in H460 cells, which when lack HRS showed maximum CER with LDFRT (4 Â 0.5 Gy) both by clonogenic inhibition and by apoptosis compared with single fraction of 2 Gy whereas the most radioresistant A549 cells had the least CER, with no significant differences between LDFRT or 2 Gy. Interestingly, in H-157 cells, a more pronounced CER was observed with LDFRT when assessed by apoptosis but clonogenic inhibition-CER was higher with 2 Gy than with LDFRT. Excluding H-157 cells, the CER by LDFRT was inversely proportional to radioresistance [(determined by D 0 , the dose to reduce survival by 67% from any point on the linear portion of the survival curve or surviving fraction (SF) at 2 Gy (SF 2 )] of the cells. LDFRT alone or in combination with cisplatin induced larger number of proapoptotic genes than 2 Gy or cisplatin þ 2 Gy in cells showing HRS when compared to H460 cells that lack HRS. These findings indicate that chemopotentiation by LDFRT is correlated more with the intrinsic radiation sensitivity of the non-small lung cancer cells than the HRS phenomenon whereas the mode of cell killing is both through apoptosis and clonogenic inhibition. Mol Cancer Ther; 10(2); 292-302. Ó2011 AACR.

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“…HRS has been shown in asynchronous populations of V79 (Marples and Joiner, 1993;Skarsgard et al, 1994) and in synchronised and asynchronous populations of T98G (Short et at., 1999a(Short et at., , b, 2003; the BE has also been shown in both cell lines in asynchronous populations, although for different endpoints, and only the BE in V79 has been studied in terms of bystander survival Shao et al, 2003a).…”

Section: Relationship Between Be and Hrsmentioning

confidence: 99%

Low-Dose Hypersensitivity and Bystander Effect are Not Mutually Exclusive in A549 Lung Carcinoma Cells after Irradiation with Charged Particles

Heuskin¹,

Wéra²,

Riquier³

et al. 2013

Radiation Research

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It is believed that irradiation interacts with biological tissues to break or modify the DNA, which is the molecule contained in the nuclei of cells that carries all the relevant information for the organism. As such, radiation is dangerous for individuals; however, its properties can also be used in medicine, e. g. in cancer treatments. Nevertheless, the exact mechanisms of cellular response to radiation are not fully understood yet, especially for low doses (below 50 cGy), where non-targeted effects, i. e. that do not involve only the interactions radiation-DNA, are taking place. In order to deepen the knowledge of those non-targeted effects, a computer model of a population of cells irradiated in vitro was written, taking into account the phenomena in the low dose domain.As a start, two non-targeted effects were studied, the bystander effect and the low dose hyperradiosensitivity. The program was written in C++ and the technique of the cellular automaton was used. The clonogenic assay was reproduced; cells were seeded in a dish and if the colony they formed after a given period of time was bigger than 50 cells, the seeded cells were assumed to have survived. The direct effect of radiation was calculated by the traditional linear quadratic model and in addition cells were subjected to the bystander effect.Some simulations were run in the case of two cell lines, the hamster cell line V79 and the glioma cell line T98G. The results show that the bystander effect is unlikely to be limited to one period of the cell cycle, but that the low dose hyper-radiosensitivity and the bystander effect could be the same phenomenon. This work also suggests that the bystander effect may be significant after low doses of conventional radiotherapy. Such a model represents a very useful tool for solving problems that at the moment cannot be investigated experimentally.

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Effects of cell cycle phase on low-dose hyper-radiosensitivity

Cited by 71 publications

References 15 publications

Low Dose Fractionated Radiation Potentiates the Effects of Taxotere in Nude Mice Xenografts of Squamous Cell Carcinoma of Head and Neck

Low Dose Fractionated Radiation Potentiates the Effects of Taxotere in Nude Mice Xenografts of Squamous Cell Carcinoma of Head and Neck

Low-Dose Fractionated Radiation Potentiates the Effects of Cisplatin Independent of the Hyper-Radiation Sensitivity in Human Lung Cancer Cells

Low-Dose Hypersensitivity and Bystander Effect are Not Mutually Exclusive in A549 Lung Carcinoma Cells after Irradiation with Charged Particles

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