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N H Terry

Publications and source records attributed to N H Terry.

66 records · Page 4Linked to original sources
PubMed1985

Fluorescent markers of hypoxic cells: a comparison of two compounds on three cell lines.

Two compounds, nitroakridin 3582 (NA) and a 3-nitro-naphthalimide (DM113), have been tested as potential fluorescent markers for hypoxic cells. Cellular fluorescence in three cell lines (V79-379A, WHF1B, EMT6) was measured by flow cytometry and high-performance liquid chromatography (HPLC) after incubating the cells with the drugs for various times in air or hypoxia. In all three cell lines, both drugs showed greater fluorescence in hypoxic than in oxic cells. There were, however, differences between the cell lines in respect of the magnitudes of hypoxic and oxic cell fluorescence and in the ratio of hypoxic to oxic fluorescence. Differences in hypoxic cell fluorescence were due to differences in the rate and extent of nitroreduction. Drug uptake and DNA content per cell were relatively unimportant factors in determining the magnitude of fluorescence. There was not a good correlation between cytotoxicity of the drugs and hypoxic fluorescence. Nitroakridin was more toxic to hypoxic than to aerated cells but the reverse was true for DM113. The dependence of fluorescence and radiosensitivity on oxygen concentration were compared for the three cell lines and only small differences between the "K"-curves for the two end-points were found. Two problems with the present compounds which should be addressed in designing future fluorogenic compounds as hypoxic markers were oxic cell fluorescence and leakage of fluorescent products from hypoxic cells.

Aminacrine↗
PubMed1985

Effects of hypoxia, pH, and growth stage on cell killing in Chinese hamster V79 cells in vitro by activated cyclophosphamide.

Several factors which influence the sensitivity of Chinese hamster V79 cells to cyclophosphamide (CY) have been studied in vitro in both suspension and monolayer cultures. Activated CY was obtained from the blood of mice 15 to 30 min after i.p. injection of CY (400 mg/kg). At pH 7.4, hypoxia rendered the cells more sensitive to activated CY. At lower values of pH (6.6 and 7.0), there was no difference between the sensitivities of oxic and hypoxic cells, although cells in both conditions were more sensitive to CY than at pH 7.4. Drug sensitivity was markedly affected by the stage of cell growth. Monolayer cultures were most sensitive to CY within a few hours of plating. Cultures then rapidly became less sensitive, with maximum resistance occurring between 24 and 48 h after plating, while the cells were still exhibiting rapid exponential growth. This development of resistance parallelled the formation of small colonies (2 to 4 cells), implying that intercellular contact may confer resistance to killing by activated CY.

Animals↗
PubMed1984

The sensitivity of normal stroma to fractionated radiotherapy measured by a tumour growth rate assay.

The growth rate of implanted tumours has been used as an assay for radiation injury in normal stroma. The subcutaneous tissue was irradiated in an unstimulated state and was then stimulated to produce new blood vessels by the inoculation of a syngeneic tumour 3 days after the last irradiation. Steep dose-response curves were obtained with a dose resolution of approximately 1 Gy. The time between irradiation and stimulation of the stroma by the tumour implant was shown to have no effect on tumour growth rate for times ranging from 1 h to 14 days after single doses. This functional assay of stromal damage has been used after irradiation with 1, 2, 5, 10 or 20 fractions of X-rays. Isoeffect data were well fitted by a linear-quadratic equation, for which the ratio of linear to quadratic coefficients (alpha/beta) was 6.2 +/- 0.6 Gy. This is on the high end of the range of published alpha/beta values for late reacting tissues and other stromal/vascular assays, but lower than those for all early reacting tissues. Overall treatment times ranging from 1 to 11 days were tested with the 2 and 5 fraction schedules. No effect attributable to slow repair or repopulation could be demonstrated over this period.

Animals↗
PubMed1984

RBE values and repair characteristics for colo-rectal injury after caesium 137 gamma-ray and neutron irradiation. II. Fractionation up to ten doses.

Early and late colo-rectal damage in mice have been assessed after 137Cs gamma irradiation and 3 MeV neutrons given as 1,2,5 or 10 fractions. Damage was measured by early changes in body weight, the late production of short faecal pellets and the pattern of lethality after irradiation. The data have been analysed in terms of the time course of expression of damage, fractionation effects and the RBE for neutrons over a wide range of doses per fraction (0.5-12.5 Gy neutrons, 3.5-33.5 Gy gamma rays). An initial epithelial denudation led to an early loss of weight, maximal at 11-17 days after irradiation. A dose-dependent weight reduction persisted over the animals' life-time. Deaths after localised pelvic gamma irradiation were progressive with no sharp demarcation between early or late phases of injury. The time course for lethality was qualitatively similar after neutrons. Beyond six months the rectum became constricted by fibrosis and a higher proportion of small faecal pellets was observed. At 6-15 months relatively shallow dose-response curves were obtained for this change. The sparing effect of fractionation was marked for the gamma-irradiated mice and almost absent after neutrons. A very high repair increment (11 Gy) was seen with two gamma-ray fractions of 20 Gy. At lower doses per fraction the proportion of each gamma-ray fraction recovered was 50-69% for all assays, i.e., similar to that for other normal tissues. There was a slight enhancement in the sparing effect for the late compared with the early assays over the lower dose range. The RBE was strongly dependent on dose per fraction because of the lack of reparable damage after neutrons. The RBE for both early and late effects was 5.0 at a neutron dose per fraction of 1 Gy. Extrapolation of the RBE data to lower doses, using the linear quadratic model, predicts a higher RBE for late (7.4-12.7) than for early damage (5.7-8.5) if gamma-ray doses below 5 Gy are used.

Animals↗
PubMed1983

RBE values for colo-rectal injury after caesium 137 gamma-ray and neutron irradiation. I. Single doses.

Colo-rectal damage in mice has been assessed after caesium gamma irradiation and 3 MeV neutrons given as single doses. Several assays were used, including body weight changes, faecal deformity and lethality. Dose response curves have been constructed for each assay at different times after irradiation, ranging from 10 days to 16 months. The data have been analysed in terms of the time course of expression of damage and the RBE for neutrons. An initial loss of weight at 10-20 days was presumably related to epithelial denudation, but a dose-dependent weight reduction (compared with controls) persisted over the animal's life span. Mice died progressively after localised pelvic gamma irradiation; there was no sharp demarcation between an early and late phase of lethal injury. Death resulted from intestinal stricture or stenosis. The time course for lethality was qualitatively different after neutrons, with little progression of damage between 5 and 11 months. Faecal deformity was detectable as a higher proportion of small pellets when the rectum became constricted by fibrosis. No significant faecal deformity was observed before 6 months after which time dose response curves could be obtained. The RBE for early damage (assessed at 1-3 months) was 2.2-2.7. This fell to 1.7-1.9 for late damage (determined at 10-15 months) over the range of neutron doses of 7.5-12 Gy. The need for sublethal assays allowing for sequential evaluation of radiation damage within the same animal is stressed, as is the need to compare RBE values from early and late endpoints at equivalent neutron doses.

Animals↗
PubMed1983

Modification of stromal radiosensitivity by misonidazole and WR-2721.

The radiosensitivity of normal vascular connective tissue has been assessed by measuring the growth rate of untreated tumours implanted into pre-irradiated sites. Dose response curves have been constructed from two end-points, the latent period (time for the tumours to reach a diameter of 2 mm) and the growth rate in the macroscopic range (above 4 mm). Well defined dose response curves were obtained for both end-points, with a lower dose threshold for the macroscopic growth rate. A third end-point which combined the first two was also tested, i.e., time to reach 8 mm (23 to 76 days over the dose range tested). This was found to give the steepest dose response curves overall and was therefore judged to be the best assay. Modification of the radiosensitivity of stromal tissue by misonidazole and by WR-2721 was investigated using this assay. The dose response curve for X rays plus misonidazole was similar to that for X rays alone indicating little or no radiosensitisation. WR-2721, however, significantly reduced the X-ray response indicating radioprotection by a factor of 1.8 (range 1.4-2.7). These data show that tumour implantation is an effective way of eliciting a quantifiable response in previously irradiated stromal tissue. The assay allows resolution of dose differences as small as 1 to 2 Gy.

Adenocarcinoma↗
PubMed1982

Early and late effects in mouse lung and rectum.

No higher RBE's were found for late than for early damage in mouse rectum up to 70 weeks or mouse lungs up to 48 weeks after irradiation with 3.0 MeV neutrons (4 MeV deuterons on Be). The smallest neutron doses per fraction were 1.5 and 0.6 Gy for rectal and lung irradiation, respectively. There was a suggestion of higher late RBE's for small doses per fraction in the lung. Slow repair after 2 neutron doses split by 31 days was unequivocally demonstrated in the lung, of magnitude about 1 Gy, possibly decreasing after about 40 weeks.

Animals↗
PubMed1982

Comparative studies of hypoxic-cell radiosensitization using artificially hypoxic skin in vivo.

The survival of epidermal cells in vivo has been used to assess potential radiosensitizers. Mouse skin was made acutely hypoxic for the irradiations, to give radioprotection by a factor of 2.7-3.0. Several concentrations of each drug were used to determine whether any of them were more effective sensitizers than misonidazole. The SER at each concentration was determined from radiobiological dose-response curves. The blood concentration and toxicity of the compounds were also determined. The sensitizing efficiency, assessed in several ways, indicated that only Ro 03-8799 gave significantly greater sensitization than misonidazole, and then only when assessed by comparing the compounds on the basis of equimolar blood concentrations. If the comparison of efficiency was made in terms of LD50 the ranking order change. The need for a more clinically relevant test of peripheral neurotoxicity is stressed.

Animals↗
PubMed1980

Is tumour radiosensitization by misonidazole a general phenomenon?

The response of 14 mouse tumour sub-lines to the radiosensitizing action of a large single dose of misonidazole (MISO) has been assessed by regrowth delay. In 13 of these, significant enhancement of radiation effect occurred under ambient conditions, indicating sensitization of naturally hypoxic cells. The enhancement observed (SER') varied with the radiation dose, as would be predicted for a mixed oxic/hypoxic cell population. The maximum SER' in these 13 tumours did not depend on histology or regrowth rate. The 14th tumour, a slow-growing sarcoma, was not sensitized under ambient conditions, but showed marked sensitization when clamped to produce acutely hypoxic cells. This is consistent with no hypoxic cells occurring naturally in a sarcoma with a slow rate of growth. Faster-growing variants of this tumour showed radiosensitization under ambient conditions. The slow-growing carcinoma, RH, however, appears to contain hypoxic cells and did show sensitization. The cytotoxic action of MISO was compared with the radiosensitization by administering it after irradiation in 8 of the tumour lines. In 2 tumours no cytotoxicity was observed. In the rest cytotoxicity was significant, but much smaller than the sensitization observed when MISO was administered before irradiation. These regrowth-delay data have been used to calculate hypoxic fractions in 3 ways. Estimates of hypoxic fraction ranged from less than 0.1% in the slow sarcoma to greater than or equal to 30% in several tumours. There is considerable variation in the estimate, according to the technique used.

Animals↗
PubMedDate not supplied

Cell cycle analysis of synchronized Chinese hamster cells using bromodeoxyuridine labeling and flow cytometry.

Chinese hamster ovary cells were synchronized into purified populations of viable G1-, S-, G2-, and M-phase cells by a combination of methods, including growth arrest, aphidicolin block, cell cycle progression, mitotic shake-off, and centrifugal elutriation. The DNA content and bromodeoxyuridine (BrdUrd) labeling index were measured in each purified fraction by dual-parameter flow cytometry. The cell cycle distributions determined from the DNA measurements alone (single parameter) were compared with those calculated from both DNA and BrdUrd data (dual parameter). The results show that highly purified cells can be obtained using these methods, but the assessed purity depends on the method of cell cycle analysis. Using the single versus dual parameter measurement to determine cell cycle distributions gave similar results for most phases of the cell cycle, except for cells near the transition from G1- to S-phase and S- to G2-phase. There the BrdUrd labeling index determined by flow cytometry was more sensitive for detecting small amounts of DNA synthesis. As an alternative to flow cytometry, a simple method of measuring BrdUrd labeling index on cell smears was used and gave the same result as flow cytometry. Measuring both DNA content and DNA synthesis improves characterization of synchronized cell populations, especially at the transitions in and out of S-phase, when cells are undergoing dramatic shifts in biochemical activity.

Animals↗