The Inactivation of Chinese Hamster Cells by X Rays: Synchronized and Exponential Cell Populations

Gillespie, C.J.; Chapman, J. D.; Reuvers, A. P.; Dugle, D.L.

doi:10.2307/3574271

Cited by 82 publications

(27 citation statements)

References 9 publications

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“…The requirement that the curves be exponential and parallel can be tested in excision assays, but there is seldom enough data over a wide range of doses for this test to be powerful [72]. The assumption that survival curves are exponential at high radiation doses is questionable, because there are cultured cell lines which do not show exponential survival curves [80][81][82]. The assumption that the survival curves have the same slope is questionable, because of the many in vitro studies showing that chronic hypoxia can alter cellular radiosensitivity [18,83,84].…”

Section: Assumptions Made In All Hypoxic Fraction Assay Techniquesmentioning

confidence: 99%

Tumor hypoxia: its impact on cancer therapy

1987

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The presence of radiation resistant cells in solid human tumors is believed to be a major reason why radiotherapy fails to eradicate some such neoplasms. The presence of unperfused regions containing hypoxic cells may also contribute to resistance to some chemotherapeutic agents. This paper reviews the evidence that radiation resistant hypoxic cells exist in solid tumors, the assumptions and results of the methods used to detect hypoxic cells, and the causes and nature of tumor hypoxia. Evidence that radiation resistant hypoxic cells exist in the vast majority of transplanted rodent tumors and xenografted human tumors is direct and convincing, but problems with the current methodology make quantitative statements about the magnitude of the hypoxic fractions problematic. Evidence that radiation resistant hypoxic cells exist in human tumors is considerably more indirect than the evidence for their existence in transplanted tumors, but it is convincing. However, evidence that hypoxic cells are a significant cause of local failure after optimal clinical radiotherapy or chemotherapy regimens is limited and less definitive. The nature and causes of tumor hypoxia are not definitively known. In particular, it is not certain whether hypoxia is a chronic or a transient state, whether hypoxic cells are proliferating or quiescent, or whether hypoxic cells have the same repair capacity as aerobic cells. A number of new methods for assessing hypoxia are reviewed. While there are still problems with all of the new techniques, some of them have the potential of allowing the assessment of hypoxia in individual human tumors.

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Section: Assumptions Made In All Hypoxic Fraction Assay Techniquesmentioning

confidence: 99%

Tumor hypoxia: its impact on cancer therapy

1987

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“…To obtain single-cell surviving fractions, cell multiplicity wNas corrected for by means of the followNing formula (Gillespie et al, 1975) valid for populations of singlets and doublets: f= (N-(X2 -4S (N1T 1))1/2)/2 (N-1) f-=single-cell surviving fraction S = microcolony surviving fraction N =mean multiplicity.…”

Section: Methodsmentioning

confidence: 99%

Inactivation by the mitotic inhibitor NY 3170 of human cells in vitro

Wibe¹,

Oftebro²

1979

Br J Cancer

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Summary.-Inactivation of NHIK 3025 cells by the mitotic inhibitor NY 3170 (1-propargyl-5-chloropyrimidin-2-one) was measured as loss of colony-forming ability. NY 3170 at a concentration of 0-15 mM allowed no formation of colonies after 12 days of continuous exposure to the drug.Metaphase arrest after treatment with NY 3170 was reversible if the drug was removed immediately after the onset of the arrest. When the cells were kept in mitosis by the presence of NY 3170, inactivation was complete after 8h incubation of mitotic cells with 0.4mM NY 3170.Using synchronized cell populations, it was shown that mitosis is by far the most sensitive stage of the cell cycle to inactivation by NY 3170. This leads to the suggestion that there is a connection between the inactivating and the metaphase-arresting effect of this drug.The age response curves show that after mitosis the stages in order of decreasing sensitivity to NY 3170 are: G2, late S, early S and G1. This is a similar age response to that reported for proliferating cells treated with bleomycin, whereas the mitotic inhibitors vincristine and vinblastine have shown quite different age response curves.A PREVIOUS report from our laboratory (Wibe et al., 1979) describes the inhibition of synchronized NHIK 3025 cells by treatment with NY 3170. Data demonstrating the influence of NY 3170 on the traverse of cells through the cell cycle were presented. The metaphase-arresting properties were examined in detail.The present investigation demonstrates the inactivating effects of NY 3170 on NHIK 3025 cells, with special attention to the age response. The results are compared with the previously reported (Wibe et al., 1979) cell-cycle inhibition by this drug. MATERIALS AND METHODSCell culture.-Information on the human cell line NHIK 3025 and the routines followed in handling stock cultures, as well as the chemical structure and the origin of the mitotic inhibitor, has been reported previously (Wibe et al., 1979;Gacek et al., 1979).Inactivation of single cells was measured as loss of the ability to form macroscopic colonies after 10-12 days of incubation. The medium was always changed 6-7 days after plating. The colonies were fixed in absolute ethanol and stained with methylene blue. Colonies containing more than 40 cells were scored for calculating surviving fractions. Experiments in our laboratory have shown that the plating efficiency of NHIK 3025 cells in the medium used (E2a supplied with 20% human serum and 10% horse serum) is 85-

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“…Colonies containing more than 50 cells were counted using a stereomicroscope. Plating efficiency was calculated from the number of colonies counted and the number of trypan blue-excluding cells plated and was corrected mathematically for multiplicity (Gillespie et al 1975). The cell surviving fraction of an irradiated tumour was calculated from the plating efficiency of the cells of the tumour and the mean plating efficiency of the cells of six unirradiated control tumours.…”

Section: Single Cell Survival Assaymentioning

confidence: 99%

Fraction of radiobiologically hypoxic cells in human melanoma xenografts measured by using single-cell survival, tumour growth delay and local tumour control as end points

Rofstad

Måseide²

1998

Br J Cancer

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Summary Four human melanoma xenograft lines (A-07, D-12, R-18, U-25) grown orthotopically in Balb/c nu/nu mice were characterzed with respect to the fraction of radiobiologically hypoxic cells. The purpose of the study was to establish a firm radiobiological basis for future use of the lines in the development and evaluation of non-invasive assays of tumour hypoxia. The hypoxic fractions were assessed using three different assays. the single cell survival assay, the tumour growth delay assay and the local tumour control assay, and the means + s.e.were found to be 6 ± 30%, 3 ± 1 0 and 5 ± 2%o respectively (A-07), 26 ± 50/0, 25 ± 60/o and 22 + 6%o respectively (D-12), 55 ± 9°o 65 ± 80/o and 48 ± 7°O respectively (R-1 8) and 52 ± 8%, 59 ± 7% and 47 ± 7% respectively (U-25). The three assays gave numerical values for the hypoxic fraction that were not significantly different for any of the lines. The hypoxic fraction differed significantly among the lines; the R-18 and U-25 lines showed higher hypoxic fractions than the D-12 line (P < 0.05). which in tum showed a higher hypoxic fraction than the A-07 line (P < 0.05). regardless of the assay. The wide range of the hypoxic fractions and the signfficant differences among the lines suggest that A-07. D-12. R-18 and U-25 tumours should be useful models in future studies attempting to develop non-invasive assays of tumour hypoxia.Keywords: treatment-response assay; hypoxic fraction; melanoma xenograft; radiation biology Manv human tumours develop regions of hxpoxic cells during gro,wth (Vaupel et al. 1989: 1991: Hockel et al. 1991. The fraction of hxpoxic cells differs substantially among individual tumours of the same histological tIpe (Nordsmark et al. 1994: Brizel et al. 1995: Wong et al. 1997. Hypoxia may cause resistance to radiation therapy (Coleman. 1988: Gatenbv et al. 1988: Hockel et al. 1993: Nordsmark et al. 1996: Brizel et al. 1997: Fx-les et al. 1997 and some forms of chemotherapx (Teicher. 1994) and mav promote the development of metastatic disease (Schwickert et al. 1995: Brizel et al. 1996: Hockel et al. 1996: Walenta et al. 1997 March 1998 Correspondence to: EK Rofstad treatment resistance and malignant progression (Kim et al. 1993: Fenton et al. 1995

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The Inactivation of Chinese Hamster Cells by X Rays: Synchronized and Exponential Cell Populations

Cited by 82 publications

References 9 publications

Tumor hypoxia: its impact on cancer therapy

Tumor hypoxia: its impact on cancer therapy

Inactivation by the mitotic inhibitor NY 3170 of human cells in vitro

Fraction of radiobiologically hypoxic cells in human melanoma xenografts measured by using single-cell survival, tumour growth delay and local tumour control as end points

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