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G H Harrison

Publications and source records attributed to G H Harrison.

At least 37 records · Page 2Linked to original sources
PubMed1991

Neutron dose-rate experiments at the AFRRI nuclear reactor. Armed Forces Radiobiology Research Institute.

Some in vitro and in vivo studies with neutrons have shown increased carcinogenic effectiveness following low-dose-rate or fractionated irradiation compared to acute exposure in the low-dose range. This would imply that the risk of cancer for persons exposed occupationally to low doses of neutrons is underestimated at present. The C3H 10T1/2 assay has played a major role in investigating neutron dose-rate effects. We describe three independent series of experiments addressing the question of the influence of dose rate using the AFRRI fission-neutron source with the C3H 10T1/2 cell transformation assay as well as with two mutation assays utilizing human-hamster hybrid AL cells. In the first two series, we focused on performing experiments with fission-neutron doses and dose rates similar to those for which enhancement of neoplastic transformation of C3H 10T1/2 cells was originally reported, and observed no discernible dose-rate effect. In the third series concurrent with the induction of neoplastic transformation in C3H 10T1/2 cells, we also measured mutagenesis at two loci in AL cells. Data for survival, neoplastic transformation, and mutation were obtained at two dose rates in the range of neutron doses 0.005 to 0.9 Gy. Dose-rate effectiveness factors expressed as ratios of the effect for low compared to high dose rate did not differ from one, indicating no influence of dose rate on these end points.

Animals↗
PubMed1991

Neoplastic transformation of C3H/10T1/2 cells following exposure to 120-Hz modulated 2.45-GHz microwaves and phorbol ester tumor promoter.

Some recent epidemiological studies have shown a positive association between cancer incidence and exposure to electromagnetic (EM) fields. Evidence from in vitro studies indicates that this effect could be due to synergistic interaction between EM fields and tumor promoters. However, no dose-response data related directly to carcinogenesis have been published. In this study, actively growing cultures of C3H/10T1/2 cells were exposed for 24 h to 2.45-GHz microwaves pulse-modulated at 120 Hz. Conditions of EM-field exposure were designed to simulate low-field exposures (specific absorption rate 0.1, 1, or 4.4 W/kg; the corresponding peak amplitudes were electric field 18, 56, or 120 V/m, magnetic field 0.09, 0.27, or 0.56 muT, respectively). In separate experiments, a 24-h EM-field exposure at 4.4 W/kg was preceded or followed by X irradiation at 0.5, 1, or 1.5 Gy. Cells were assayed for cell survival and neoplastic transformation with or without post-treatment administration of 0.1 micrograms/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) for the duration of the assay. The EM fields alone had no effect on cell survival or induction of neoplastic transformation. However, enhancement of transformation due to EM fields plus TPA was highly significant and ranged up to a level equivalent to that produced by 1.5 Gy of X rays. The frequency of neoplastic transformation was dependent on the level of EM exposure and was additive with doses of X rays given as a cocarcinogen.

Animals↗
PubMed1990

Heat-sensitive state of mouse mammary carcinoma cells in tumors.

The heat response of the SCK mammary carcinoma of A/J mice was studied in vivo and in vitro. Solid tumors or tumor cells in culture were heated in a water bath and cell survival was determined by clonogenicity in vitro. Cells in tumors were much more sensitive to heat than cells in culture. To eliminate vascular effects, tumors were dissociated into small fragments and the tumor fragments were heated in vitro, so that cells were heated while in contact with neighbors and in a complete medium. Cells in tumor fragments were as sensitive to heat as cells in tumors, even though vascular effects during heat exposure were excluded. The heat-sensitive tumor fragments gradually became heat resistant during 3 h of incubation in a complete medium at physiological temperature. The transition from a heat-sensitive to a heat-resistant state was not correlated with the development of thermotolerance or stress-related proteins. The transition was inhibited when the extracellular environment was made acidic or hypoxic but not when it was glucose and serum deprived. These results suggest that SCK tumor cells in vivo are sensitive to heat, and the heat-sensitive state appears to be established under the influence of the intratumor environment.

Adaptation, Physiological↗
PubMed1989

Continuous-wave ultrasound and neoplastic transformation in vitro.

C3H/10T1/2 cells in suspension were assayed using an initiation-promotion protocol for neoplastic transformation induced by continuous-wave ultrasound. Cells were insonated at 1.765 MHz for 40 min. Two ultrasonic intensities were used: 1.3 and 2.6 W/cm2 spatial average. The first intensity was found to be noncytotoxic; the second resulted in immediate lysis of 20% of the cells, followed by the clonogenic survival of 64% of the remaining cells. Ultrasound was delivered alone or in combination with X-rays (2 Gy, 240 kVp given before ultrasound), and/or 12-O-tetradecanoyl-phorbol-13-acetate (TPA, 0.1 microgram/ml post-irradiation). Under all treatment conditions, there was no effect of ultrasound on transformation at the 95% confidence level.

Animals↗
PubMed1989

Induction of neoplastic transformation in C3H/10T1/2 cells by 2.45-GHz microwaves and phorbol ester.

C3H/10T1/2 cells were exposed to 2.45-GHz microwaves for 24 h and/or 1.5 Gy of 238-kVp X rays at 3.75 Gy/min. Transformation frequency and cell survival were measured with or without postirradiation addition of the tumor promoter tetradecanoyl-phorbol-13-acetate (TPA) at 0.1 microgram/ml. We previously reported (Carcinogenesis 6,859-864, 1985) an enhancement of transformation frequency when 10T1/2 cells exposed to a special sequence of microwaves and X rays were subsequently cultured in TPA. The same sequence of microwaves and X rays without promotion resulted in a transformation response similar to that induced by X rays alone. We now report statistically significant (at P greater than 0.999) enhancement of transformation response by TPA in cells exposed to 2.45-GHz microwaves (SAR = 4.4 W/kg). Microwaves alone had no effect on transformation. Plating efficiency and cell survival were not affected by TPA or microwave treatments.

Animals↗
PubMed1988

Effect of X-ray dose protraction and a tumor promoter on transformation induction in vitro.

We have investigated the effects of X-rays given in a brief exposure (1 min or less) or protracted over 5 h, on cell survival and the induction of neoplastic transformation in C3H/10T1/2 cells with an emphasis on latent transformation damage remaining after protracted irradiation. This latent damage and its expression were investigated at accumulated doses of 0.25 to 4 Gy by chronic treatment with TPA (12-O-tetradecanoyl-phorbol-13-acetate or phorbol myristate acetate) at 0.1 microgram/ml beginning after irradiation. Transformation incidence from protracted as well as brief X-irradiations was linearly related to X-ray dose in the presence of 0.1 microgram/ml TPA/ml. In the absence of TPA, the best fits were obtained with cubic rather than quadratic functions. The effect-modifying factors due to dose protraction were similar with or without TPA and averaged 4.6 at low doses (up to 2 Gy). Also within this dose range average transformation enhancement due to TPA was approximately 4. Our results indicate that dose protraction does not change the shape the dose-response curve for transformation, and that the shape change induced by TPA is also independent of dose protraction.

Animals↗
PubMed1988

Lack of inverse dose-rate effect on fission neutron induced transformation of C3H/10T1/2 cells.

Exponential and density-inhibited cultures of C3H/10T1/2 cells were exposed to a single dose of 0.3 Gy of fission neutrons delivered at rates ranging from 0.005 to 0.1 Gy/min. No discernible effect upon cell survival or transformation was observed by a lowering of the fission neutron dose rate in either exponential or plateau cultures. At the level of 2.3 x 10(-4) transformants per surviving cell, the RBE for neoplastic transformation was three at acute dose rates and ten at the lowest dose rate studied (0.005 Gy/min for neutrons and 0.01 Gy/min for X-rays).

Animals↗
PubMed1987

Experimental demonstration of Fourier synthesis of an annular ultrasonic intensity distribution.

Ultrasonic source velocity distributions can be manipulated to provide beam shaping, as demonstrated by much previous work on focussing, side-lobe reduction and the production of Gaussian beam profiles. In principle, other beam profiles can be specified to order using inverse source calculations. We have presented a Fourier optics calculation for the source velocity distribution required to produce a desired distribution in intensity at a given axial distance. In this Paper, we present experimental verification of this approach using a 3.8 cm radius lead metaniobate transducer divided into 10 annuli of equal width, operated at 850 kHz continuous wave. The radiofrequency (RF) voltages supplied to each annulus were adjusted to approximate a source distribution calculated to produce an annular intensity distribution with inner and outer radii of 1.5 and 2.5 cm, respectively, at an axial distance of 30 cm in water. Good experimental verification of predicted intensities was achieved.

Fourier Analysis↗
PubMed1987

Repair time for oncogenic transformation in C3H/10T1/2 cells subjected to protracted X-irradiation.

With exponential cultures of C3H/10T1/2 cells, we have investigated the effect of X-ray dose protraction on oncogenic cell transformation in the dose range 0.25-2 Gy. Within a particular experiment a constant exposure time was used. In different experiments exposure time varied between 1 and 5h. Cell transformation was analysed using the linear-quadratic relation, gamma (D) = alpha 1D + alpha 2D2, between transformation frequency per surviving cell and X-ray dose. Based on values of the linear coefficients, we developed an empirical formula for relating slopes of dose induction curves obtained at high or reduced dose rate condition. Our estimate of repair half-time for cell transformation with 95 per cent confidence limits is 2.4 (1.8, 3.0) h.

Animals↗
PubMed1985

Far-field 2.45 GHz irradiation system for cellular monolayers in vitro.

A 2.45-GHz microwave exposure facility was developed for long-term TEM irradiation of cellular monolayers. Culture flasks with cells attached to the inside bottom surface were filled with medium, submerged in a 60 X 60 X 12-cm water bath on the field central axis, and exposed in the far-field 2 m below the ceiling-mounted antenna. A quarter-wave transformer plate increased the power transmitted into the water bath, and treatment temperatures were maintained by closed circulation with an external temperature control reservoir. Power density mapped below the quarter-wave plate indicated uniform TEM fields in the 25 X 25-cm region where flasks were located. With 1 kW of forward power to the antenna, the SAR [W/kg] = 45 exp(-0.607d) where d [cm] is the depth in water at any point within this area.

Animals↗
PubMed1985

Evidence for microwave carcinogenesis in vitro.

We investigated the carcinogenic activity of 2.45 GHz microwave radiation (MW) combined with benzo[a]pyrene (BP) or X-rays, using an in vitro assay for malignant transformation in C3H/10T1/2 mouse-embryo fibroblasts. Additional experiments were performed to assess the effect of a non-cytotoxic and non-transforming concentration of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on transformation induction in cells treated with MW and X-rays. Experiments were performed at low incident power density, corresponding to an energy absorption rate of 4.4 W/kg. Cells were treated at 37.2+/-0.1 degree C. MW reduced the plating efficiency of 50%, while TPA increased it by 40%. MW had no effect on transformation induced by BP or X-rays in the absence of tumor promoter. TPA treatment of cells previously irradiated with MW and X-rays yielded a statistically significant 3.5- or 1.6-fold increase in transformation when compared with the transformation frequency of cells previously irradiated with X-rays alone at 1.5 and 4.5 Gy, respectively. Our results suggest that low-level 2.45 GHz MW radiation can induce latent transformation damage which can then be revealed by the action of tumor promoters.

Animals↗
PubMed1985

Survival and oncogenic transformation of C3H/10T1/2 cells after extended X irradiation.

We performed two independent series of experiments aiming at establishing dose-response curves for lethality or oncogenic transformation in vitro following acute and protracted X-ray doses between 0.25 and 2 Gy. In the first series of experiments, we measured the survival of C3H/10T1/2 CL8 fibroblasts and their transformed counterparts (MCA TCL15) as a function of X-ray dose delivered at 0.49 Gy/min. In addition, 1- and 2-Gy doses were split into four fractions separated by 3-h intervals. The accuracy of survival fraction measurements was about 2%. We found that the dose-response curve at 0.49 Gy/min was a linear function of the dose for both cell lines with a negative slope of 0.171 +/- 0.007 Gy-1 or 0.160 +/- 0.003 Gy-1 for 10T1/2 or MCA cells, respectively, indicating a similar initial radiosensitivity of normal and transformed 10T1/2 cells. Dose fractionation resulted in a significant increase of the survival, relative to that measured when X-ray dose was delivered in a single fraction. The enhancement of survival was not, however, significantly different for 10T1/2 and MCA cells, indicating similar cellular repair abilities. In the second series of experiments, we measured oncogenic transformation in vitro (along with the survival) of C3H/10T1/2 cells, using a constant exposure time technique in which the dose rate was proportional to the total dose so that the repair time was equal at all dose levels. The dose-response curves for oncogenic transformation in the low-dose range between 0.25 and 2 Gy were consistent with a linear response with a positive slope 2.50 +/- 0.11 X 10(-4), 1.50 +/- 0.03 X 10(-4), or 0.87 +/- 0.05 X 10(-4) Gy-1, for acute, 1-h, or 3-h protracted exposures, respectively. Hence, relative to the acute irradiation, the 1- or 3-h protraction of the X-ray dose reduced the slopes by 0.60 +/- 0.03 or 0.35 +/- 0.03, respectively. These results indicate that in the dose range between 0.25 to 2 Gy, the dose-response curves for survival or oncogenic transformation were linear and can be modified by the temporal distribution of the X-ray dose.

Animals↗
PubMed1983

Oncogenic transformation of C3H/10T1/2 cells by X-rays, fast-fission neutrons, and cyclotron-produced neutrons.

Lethality and oncogenic transformation were measured in C3H/10T1/2 murine fibroblasts exposed to neutrons and X-rays at doses between 0.5 and 11 Gy. Transformation results with X-rays and low-energy, reactor-produced neutrons were used as a baseline to compare and evaluate the results obtained with high-energy, cyclotron-produced neutrons. The radiations were 100-kVp X-rays at 0.49 Gy min-1, reactor fission neutrons at 0.10 to 0.31 Gy min-1 with an 8 to 20 per cent gamma dose component, and cyclotron-produced neutrons at 0.51 Gy min-1 with mean energy 38 MeV and an 8 per cent gamma dose component. The radiobiological effectiveness (r.b.e.) for cell lethality was 2.4 +/- 0.2 for fission neutrons and 1.7 +/- 0.1 for high-energy neutrons. The maximum proportions of transformants per thousand surviving cells were, respectively, 3.7 +/- 0.8, 6.5 +/- 0.7, and 2.3 +/- 0.6 for X-rays, fission neutrons, and cyclotron-produced neutrons. The maximum observed r.b.e. for transformation induction was 3.8 for fission neutrons and 1.2 for cyclotron neutrons. Thus, high-energy neutrons exhibit a higher r.b.e. for cell killing capacity than for oncogenic transformation in C3H/10T1/2 cells.

Animals↗
PubMed1983

Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers.

Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +/- 0.2, compared with an oxygen enhancement ratio of 3.3 +/- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +/- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD50 was estimated to be 125-150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +/- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit.

Adenocarcinoma↗
PubMed1982

Thin-layer liquid crystal thermometry of cells in vitro during hyperthermal microwave irradiation.

A nonperturbing technique of thin-layer liquid crystal thermometry was developed to quantitate heating of Chinese hamster ovary cells and the bacterium Serratia marcescens when exposed to 2450-MHz microwave fields at 0.2-0.5 W/cm2. Cells suspended in culture medium were injected into 5-cm glass microcapillary tubes coated on the inside with a thin layer of liquid crystal. The tubes were sealed and placed parallel to the electric field in a watertight waveguide exposure chamber where they were heated by circulating temperature-controlled water. Even at high circulation rates, liquid crystal color changes indicated local microwave capillary tube heating of 0.1-0.25 degrees C. Precision of measurement was 0.02 degrees C. Observations during microwave heating were significantly different from observations without microwaves at the 1% level, and heating increased as circulating water flow was reduced from 300 ml/s to 100 ml/s. The results of a cell survival assay following hyperthermal treatment were in good agreement with expectations based on the observations of microwave heating using liquid crystals.

Animals↗