The distribution in the cell cycle of normal cells and of irradiated tumour cells in mice

Raju, M. R.; Trujillo, T. T.; Mullaney, P. F.; Romero, Alfonso E.; Steinkamp, John A.; Walters, R.A.

doi:10.1259/0007-1285-47-559-405

Cited by 17 publications

(5 citation statements)

References 11 publications

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“…Cell lines divide actively whereas most of the cells in a tissue are in resting phase, G 0 [38]. Glioma cell lines have been shown to possess a less efficient DNA repair capacity as compared to normal human astrocytes [39].…”

Section: Introductionmentioning

confidence: 99%

Efficiency of nonhomologous DNA end joining varies among somatic tissues, despite similarity in mechanism

Sharma

Choudhary

Raghavan

2010

Cell. Mol. Life Sci.

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Failure to repair DNA double-strand breaks (DSBs) can lead to cell death or cancer. Although nonhomologous end joining (NHEJ) has been studied extensively in mammals, little is known about it in primary tissues. Using oligomeric DNA mimicking endogenous DSBs, NHEJ in cell-free extracts of rat tissues were studied. Results show that efficiency of NHEJ is highest in lungs compared to other somatic tissues. DSBs with compatible and blunt ends joined without modifications, while noncompatible ends joined with minimal alterations in lungs and testes. Thymus exhibited elevated joining, followed by brain and spleen, which could be correlated with NHEJ gene expression. However, NHEJ efficiency was poor in terminally differentiated organs like heart, kidney and liver. Strikingly, NHEJ junctions from these tissues also showed extensive deletions and insertions. Hence, for the first time, we show that despite mode of joining being generally comparable, efficiency of NHEJ varies among primary tissues of mammals.

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Section: Introductionmentioning

confidence: 99%

Efficiency of nonhomologous DNA end joining varies among somatic tissues, despite similarity in mechanism

Sharma

Choudhary

Raghavan

2010

Cell. Mol. Life Sci.

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“…The cell cycle analysis demonstrated that treatment with RECA did not change the life cycle of differentiated hWJMSCs, regardless of whether it was induced by RECA alone or RECA in combination with NF. Both the differentiated and undifferentiated hWJMSCs exhibited a normal cell cycle pattern, in contrast to tumor cells, which have a high percentage of cells in the S-phase [56]. The cell distribution showed that cells were mainly in the G 0 /G 1 phase in the present study, which could be attributed to the confluent state of the cells following induction and/or the inhibitory effects of RECA itself [57].…”

Section: Discussionmentioning

confidence: 60%

The effects of Centella asiatica (L.) Urban on neural differentiation of human mesenchymal stem cells in vitro

Omar

Lokanathan

Razi

et al. 2019

BMC Complement Altern Med

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Background Centella asiatica (L.) Urban, known as Indian Pennywort, is a tropical medicinal plant from Apiaceae family native to Southeast Asian countries. It has been widely used as a nerve tonic in Ayuverdic medicine since ancient times. However, whether it can substitute for neurotrophic factors to induce human mesenchymal stem cell (hMSCs) differentiation into the neural lineage remains unknown. This study aimed to investigate the effect of a raw extract of C. asiatica (L.) (RECA) on the neural differentiation of hMSCs in vitro. Methods The hMSCs derived from human Wharton’s jelly umbilical cord (hWJMSCs; n = 6) were treated with RECA at different concentrations; 400, 800, 1200, 1600, 2000 and 2400 μg/ml. The cytotoxicity of RECA was evaluated via the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) and cell proliferation assays. The hWJMSCs were then induced to neural lineage for 9 days either with RECA alone or RECA in combination with neurotrophic factors (NF). Cell morphological changes were observed under an inverted microscope, while the expression of the neural markers S100β, p75 NGFR, MBP, GFAP and MOG was analyzed by quantitative polymerase chain reaction and immunocytochemistry. The cell cycle profile of differentiated and undifferentiated hWJMSCs was investigated through cell cycle analysis. Results RECA exerted effects on both proliferation and neural differentiation of hWJMSCs in a dose-dependent manner. RECA reduced the proliferation of hWJMSCs and was cytotoxic to cells above 1600 μg/ml, with IC 50 value, 1875 ± 55.67 μg/ml. In parallel with the reduction in cell viability, cell enlargement was also observed at the end of the induction. Cells treated with RECA alone had more obvious protein expression of the neural markers compared to the other groups. Meanwhile, gene expression of the aforementioned markers was detected at low levels across the experimental groups. The supplementation of hWJMSCs with RECA did not change the normal life cycle of the cells. Conclusions Although RECA reduced the proliferation of hWJMSCs, a low dose of RECA (400 μg/ml), alone or in combination of neurotrophic factors (NF + RECA 400 μg/ml), has the potential to differentiate hWJMSCs into Schwann cells and other neural lineage cells. Electronic supplementary material The online version of this article (10.1186/s12906-019-2581-x) contains supplementary material, which is available to authorized users.

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“…This demonstrates also that in this tumor only a fraction of the cells are able to progress through the cell cycle. In other tumors the radiation-induced G2 block could be observed more easily, probably because of a larger amount of cycling cells (16,18).…”

Section: Continuous Labeling Of Tumor and Host Cells By Brdurd Using mentioning

confidence: 99%

“…Blocks at certain stages of the cycle, recruitment of resting cells into the proliferating component, and variations in the length of the G1-, S-and G2-phases are important effects induced in the tumor by irradiation. The knowledge of such data is critical to the identification of the dynamic processes that determine how the tumor as a whole responds to irradiation.Flow cytometric techniques as well as labeling techniques with radioactive DNA precursors are widely used to study cell cycle kinetics in cells in tumors (11,12,15,16,(18)(19)(20)(21). Besides technical problems, the main …”

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confidence: 99%

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Cell cycle kinetic measurements in an irradiated rat rhabdomyosarcoma using a monoclonal antibody to bromodeoxyuridine

Nüsse¹,

Afzal²,

Carr³

et al. 1985

Cytometry

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Cell cycle kinetics after X-irradiation were studied in a solid rat rhabdomyosarcoma using a monoclonal antibody to bromodeoxyuridine (BrdUrd) in cells in which the DNA was labeled by BrdUrd. It could be shown that this tumor was composed of about 80% diploid host cells, and only 20% of the cells in the dissociated tumor were actually tetraploid tumor cells. When rats were injected intraperitoneally with BrdUrd to label S-phase cells in the tumor, only a fraction of both tqpes of cells became labeled with BrdUrd during Sphase, even 24 h after injection. The diploid BrdUrd-labeled cells progressed rapidly into cycle; 4 h after injection of BrdUrd, labeled diploid G1-phase cells could be observed. Only 25% of the tetraploid S-phase cells could be labeled by a single injection of BrdUrd (160 mgkg body weight). These labeled tetraploid cells progressed through the cell cycle with similar velocities as did labeled diploid cells. Using a "Mini Osmotic Pump" containing bromodeoxycytidine (BrdCyd) at high concentration (0.3 mol/L) that released BrdCyd continuously into the organism where it was converted to BrdUrd, it could be shown that after 2 days about 60% of cells in S-phase and 70% of cells in G2-phase were labeled. The fraction of labeled G2-phase cells in irradiated tumors (D = 10 and 20 Gy) was enhanced between 10 and 50 h after irradiation due to a radiation-induced G2 block in cycling tetraploid tumor cells. No effect of irradiation on incorporation of BrdUrd in S-phase could be observed in the continuous labeling experiments in contrast to the pulse labeling with RrdUrd, where a small retardation of DNA synthesis was observed in the irradiated tumors during the first 15 h after irradiation. When dissociated cells of the tumor were plated in medium containing 20 pmol/L BrdUrd, only the tetraploid tumor cells were able to incorporate BrdUrd and to enter cycle.Key terms: Tumor cell cycle kinetics, flow cytometry, monoclonal antibody to BrdUrd, X-ray irradiation, continuous labeling with bromodeoxycytidineThe response of a rat rhabdomyosarcoma system to irradiation with heavy charged particles and X-rays has been extensively investigated previously with experiments conducted both in vivo and in vitro (5)(6)(7)(22)(23)(24). The radiobiological end-points studied included tumor volume response (22,231, cell survival after tumor irradiation in situ (24), and survival of oxic and hypoxic cells irradiated and assayed in vitro (7). It is known that the redistribution of cells within the cell cycle after irradiation is a n important factor affecting the speed of tumor regrowth. Therefore, measurement of the movement of both the total and the clonogenic population of tumor cells in vivo through the cell cycle as a function of time after irradiation is of special interest in this context. Blocks at certain stages of the cycle, recruitment of resting cells into the proliferating component, and variations in the length of the G1-, S-and G2-phases are important effects induced in the tumor by irradiation. The knowledge of s...

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The distribution in the cell cycle of normal cells and of irradiated tumour cells in mice

Cited by 17 publications

References 11 publications

Efficiency of nonhomologous DNA end joining varies among somatic tissues, despite similarity in mechanism

Efficiency of nonhomologous DNA end joining varies among somatic tissues, despite similarity in mechanism

The effects of Centella asiatica (L.) Urban on neural differentiation of human mesenchymal stem cells in vitro

Cell cycle kinetic measurements in an irradiated rat rhabdomyosarcoma using a monoclonal antibody to bromodeoxyuridine

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