Radiation Sensitivity of Human Malignant Lymphocytes

Seshadri, Ram; Matthews, Chris; Morley, Alexander A.

doi:10.3109/02841868509134410

Cited by 8 publications

(6 citation statements)

References 9 publications

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“…It is possible that the cells have reverted to the sensitive phenotype because of the prolonged period in cell culture. This heightened drug sensitivity is in contrast to a previous study [14] in relation to radiation sensitivity, wherein we observed that the malignant lymphocytes had a significant ability to repair ionizing radiation damage. It may be argued that the relative resistance of normal T lymphocytes to cytotoxic drugs is due to a large number of cells existing in the resting phase of the cell cycle.…”

Section: Discussioncontrasting

confidence: 99%

“…The most im- portant features of cloning in microwells are the improved cloning efficiency and the ease with which the cells arising from the clones can be used for further analysis. Hence, we were able to determine the clone survival after irradiation [14] and after exposure to cytotoxic drugs, as shown in this report, down to a fraction of less than 0.001. We were also able to show that the clones surviving the exposure to the highest concentration of drugs are true drug-resistant mutants [4].…”

Section: Discussionmentioning

confidence: 63%

See 1 more Smart Citation

In Vitro Cytotoxic Drug Sensitivity of Human Normal and Malignant Lymphocyte‐Clone‐Forming Cells

Matthews

Kutlaca

Seshadri

1987

The International Journal of Cell Cloning

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Cytotoxic drug sensitivity of normal human lymphocytes and malignant lymphocytes was estimated by a clonogenic method. Malignant T and B lymphocytes were relatively more sensitive than normal T lymphocytes to vincristine and Adriamycin. Since no plateau was observed in the clone survival with associated increasing drug concentration, spontaneous mutants could not be detected. It is suggested that the resistance to "natural product" drugs such as vincristine arises from induced mutations and not from the selection of already existing spontaneous mutants.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 63%

In Vitro Cytotoxic Drug Sensitivity of Human Normal and Malignant Lymphocyte‐Clone‐Forming Cells

Matthews

Kutlaca

Seshadri

1987

The International Journal of Cell Cloning

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“…These results lead to the following conclusions: (i) A pronounced radiation effect can be detected when analyzing the rate of dicentric chromosomes in CAL 33 cells after 2 Gy γ-irradiation; (ii) compared to normal human lymphocytes the spontaneous rate of dicentric chromosomes is significantly higher ( p < 0.05; Fishers’ exact test) and (iii) the HNSCC cell line CAL 33 is less sensitive to ionizing radiation when compared to normal human lymphocytes. The resulting survival curve of CAL 33 HNSCC cells is in good concordance to published data [72] and several earlier studies already confirmed high radiation sensitivities for human lymphocytes [78,79,80]. The obtained data of CAL 33 cells can serve as a starting point for the determination of radiosensitivity of genetically engineered cell culture models based on this cell line.…”

Section: Resultssupporting

confidence: 88%

Establishment and Molecular Cytogenetic Characterization of a Cell Culture Model of Head and Neck Squamous Cell Carcinoma (HNSCC)

Bauer

Hieber

Schaeffner

et al. 2010

Genes

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Cytogenetic analysis of head and neck squamous cell carcinoma (HNSCC) established several biomarkers that have been correlated to clinical parameters during the past years. Adequate cell culture model systems are required for functional studies investigating those potential prognostic markers in HNSCC. We have used a cell line, CAL 33, for the establishment of a cell culture model in order to perform functional analyses of interesting candidate genes and proteins. The cell line was cytogenetically characterized using array CGH, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). As a starting point for the investigation of genetic markers predicting radiosensitivity in tumor cells, irradiation experiments were carried out and radiation responses of CAL 33 have been determined. Radiosensitivity of CAL 33 cells was intermediate when compared to published data on tumor cell lines.

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“…It has been suggested that the mutation rates of different cells might be affected by different cellular growth rates. 25 The numbers of cell divisions occurring during the expansion phases of uveal melanoma are likely higher for small tumors, ie, when the tumor initially starts growing (eFigure in the Supplement), because doubling time of tumor cells lengthens as the tumor grows. 26 Before a tumor becomes detectable at 10 9 cells (ie, 1 g) it must undergo approximately 30 population doublings.…”

Section: Discussionmentioning

confidence: 99%

Association of Uveal Melanoma Metastatic Rate With Stochastic Mutation Rate and Type of Mutation

et al. 2018

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Importance: To understand the mechanisms of metastasis of uveal melanoma in order to advise patients and develop treatments for this tumor. Objective: The purpose of this study was to examine the stochastic properties of primary uveal melanoma including the mutation rate as a function of tumor size and metastatic rate relative to the type of mutation. Data sources, Study Selection, Main Outcome and Measures: We computed the mutation rate in different sized uveal melanomas using previously published large datasets. Tumor volume was estimated using the spherical cap method. We also calculated the metastatic rate using an updated dataset of uveal melanoma patients with known mutations in BAP1, SF3B1 and EIF1AX provided by the Rotterdam Ocular Melanoma Study Group. Results: Based on the 5-year metastatic rates, mutation rates ranged from 1.09 X 10−8 to 7.86 X 10−7 per cell division, using our calculation algorithm. A higher mutation rate was found for tumors with smaller thicknesses. EIF1AX mutations were not exclusive of other mutations as two cases with EIF1AX mutations and metastasis also had BAP1 mutations. None of the tumors with only an EIF1AX mutation metastasized. After plotting the yearly metastatic rate versus time after treatment, we observed a small peak at 1 year and a large peak at 3.5 years after treatment for BAP1 mutations, with peaks between 2 and 3 years and at 7 years for SF3B1 mutations. Conclusions and Relevance: We observed a higher mutation rate for smaller tumors, which may be explained by a greater number of cell divisions occurring during the expansion phase of smaller uveal melanomas. Regarding time to clinically detected metastases, the first two peaks appear to relate to BAP1-mutated tumors and the late peak to SF3B1-mutated tumors.

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Radiation Sensitivity of Human Malignant Lymphocytes

Cited by 8 publications

References 9 publications

In Vitro Cytotoxic Drug Sensitivity of Human Normal and Malignant Lymphocyte‐Clone‐Forming Cells

In Vitro Cytotoxic Drug Sensitivity of Human Normal and Malignant Lymphocyte‐Clone‐Forming Cells

Establishment and Molecular Cytogenetic Characterization of a Cell Culture Model of Head and Neck Squamous Cell Carcinoma (HNSCC)

Association of Uveal Melanoma Metastatic Rate With Stochastic Mutation Rate and Type of Mutation

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