Carcinogenicity of radon/radon decay product inhalation in rats--effect of dose, dose rate and unattached fraction.

PURPOSE: The effects of inhalation of radon/radon decay products at different total doses, dose rates and 'unattached' fractions were investigated in a life span study in rats. MATERIALS AND METHODS: 1574 rats inhaled radon/radon decay products in a purpose-built recirculating exposure system that provided stable/reproducible exposure conditions. 501 were maintained as controls. RESULTS: Lung tumour incidences were significantly elevated in most exposed groups. The study power was insufficient to resolve the shape of the dose and dose rate response curves, but combination of this data with that from other studies demonstrated that for high cumulative exposures, the lifetime excess absolute risk increases with increasing exposure durations and for low cumulative exposures the opposite trend occurs. Exposure did not increase leukaemia incidences. A small number of non-lung tumour types including mammary fibroadenoma showed elevated incidences in some exposed groups, however not consistently across all exposure groups and showed no dose or dose rate relationship. CONCLUSIONS: Radon/radon decay product exposure caused excess lung tumours in rats along with limited non-lung effects. The results are consistent with the findings that at low cumulative exposures decreasing exposure concentrations or protracting the time over which the dose is delivered, reduces lung tumour risk. At higher levels, decreasing exposure concentrations or protracting exposure time increases lung tumour risk.

Purification of recombinant green fluorescent protein using chromatofocusing with a pH gradient composed of multiple stepwise fronts.

Green fluorescent protein (GFP), which fluoresces in the green region of the visible spectrum and is widely used as a reporter for gene expression and regulation, was overexpressed in the JM105 strain of Escherichia coli transformed with pBAD-GFP. A two-step chromatofocusing procedure was used to purify GFP starting from cell lysate, with each step employing a pH gradient extending from pH 5.5 to 4.0. The first chromatofocusing step was performed using a low-pressure column in which a retained stepwise pH front formed by adsorbed buffering species was used to capture GFP directly from clarified cell lysate and selectively focus it into a chromatographic band. The second step utilized a high-performance column under mass overloaded conditions where a similar pH front acted as a protein displacer and led to the formation of a highly concentrated rectangular band of GFP. The overall procedure yielded a 50-fold increase in purity, a 20-fold volume reduction, and a recovery and purity for GFP of 60% and 80%, respectively. Because the method employs a strong-base ion-exchange column packing and low-cost buffers formed with formic and acetic acids instead of the proprietary column packings and polyampholyte elution buffers more generally used for chromatofocusing, it appears to be a practical alternative for the preparative ion-exchange chromatography of GFP in particular and for the recovery of recombinant proteins from cell lysate in general. A discussion is also given concerning the choice of appropriate buffers for the rational design of pH gradients involving retained, stepwise pH fronts that span a given pH range and of the use of the fluorescence properties of GFP for flow visualization and chromatographic process development.

Effects of continuous inhalation exposure of rats to radon and its progeny at various levels of dose and dose rate: interim results.

Studies of rats at Harwell and CEA [Monchaux et al., Radiat. Res. 152 (Suppl.), S137-S140, 1999] are currently in progress to determine the factors affecting the risk of induction of lung tumors after exposure to radon and radon progeny. Knowledge of the effect of dose, dose rate and characteristics of the aerosol on lung tumor induction in rats may be used to improve estimates of risk from domestic exposure. At Harwell, three studies are in progress, studying the effect of dose, dose rate, and dose rate at low total exposures. Approximately 2000 adult male rats have been exposed. A small number of rats were taken to determine deposition in the respiratory tract and the early effects of exposure on cell proliferation and nuclear aberrations. The remaining animals have been held for their life span. To date 65% of the animals in the first study have been examined. Current results (for 421 rats) suggest that exposure to radon and radon progeny causes elevated incidences of both benign and malignant lung tumors. These findings are based on incomplete tumor incidences. Competing causes of death may affect the results, and full statistical analysis is required before firm conclusions can be drawn about the effect of dose and dose rate.

Displacement chromatography of proteins using a self-sharpening pH front formed by adsorbed buffering species as the displacer.

The preparative-scale separation of two proteins into adjoined, pure bands was accomplished using a novel, hybrid chromatography method which employs chromatofocusing using a self-sharpening pH front and displacement development. The method eliminates the use of a traditional displacer for accomplishing displacement chromatography, and was used to separate the A and B forms of beta-lactoglobulin using a strong-base anion-exchange column packing and a buffer system composed of acetic acid and either 3-(N-morpholino)propane-sulfonic acid (MOPS) or 2-(N-morpholino)ethanesulfonic acid (MES). Sample loads up to 150 mg of protein were applied to a 75 x 7.5 mm column to produce a displacement train composed of highly pure protein bands with greater than 90% recovery of protein. A discussion is given of the chromatographic behavior of proteins under concentration overloaded conditions for the case where a self-sharpening pH front formed using adsorbed buffering species is used to desorb proteins from an anion-exchange column packing.

Experimental and numerical studies of the chromatofocusing of dilute proteins using retained pH gradients formed on a strong-base anion-exchange column.

The separation of dilute protein mixtures was achieved using simple monovalent buffering species to form retained, internally produced pH gradients on a strong-basic anion-exchange column. Highly focused proteins bands localized on stepwise pH transitions were produced experimentally under trace and volume overloaded feed conditions. Numerical simulations were performed that accurately predict the pH profile and protein band shapes in the column effluent. Experimental results were combined with numerical investigations to explore strategies for designing efficient preparative-scale chromatofocusing systems using simple, inexpensive buffers and adsorbents.

Intercomparison of measurement techniques used in radon exposure facilities for animals in Europe.

The biological effects of exposure to radon and its progeny are being studied in animals by three laboratories in Europe. The facilities used for such exposures are described, together with the methods used to estimate radon progeny concentrations and the activity deposited in the lungs of exposed animals. As the facilities and methods vary, a series of comparison exercises has been carried out at the three facilities; CEA/COGEMA, Razes, France, TNO, Rijswijk, The Netherlands and AEA Technology, Harwell, U.K. The results of the exercise are presented together with reasons for the discrepancies in results between the groups thus ensuring that estimates of exposure provided by the groups for their studies is directly comparable.

The particle size distribution of technegas and its influence on regional lung deposition.

The size distribution of the aerosol produced by a technegas generator has been measured with a screen diffusion battery. The median diameter of the active aerosol was found to be of the order 140 nm and not to vary with the delay between generation and use. The measurements indicate that about 20% of the aerosol should be deposited in deep lung with about 5% deposited in the upper airways.

Metabolism of some industrial uranium tetrafluorides after deposition in the rat lung.

UNLABELLED: Two commercially produced natural uranium tetrafluorides were administered to rats either by inhalation or direct injection into the lungs. THE RESULTS: show that, for both materials uranium is cleared rapidly from the lungs, much of it to the blood, show that the distribution of uranium amongst body tissues, and the fraction of the systemic content excreted in urine, is similar to that obtained after the administration of U(VI) bicarbonate, show that the transportability of uranium is much greater than in previously reported studies with other preparations of uranium tetrafluoride, suggest that lung radioactivity counting measurements would be of limited value for interpreting human exposures, indicate that for setting exposure limits these tetrafluorides should be considered moderately transportable compounds (ICRP inhalation class W).

Decorporation of inhaled americium-241 dioxide and nitrate from hamsters using ZnDTPA and Puchel.

Accidental intakes of 241AmO2 and 241Am(NO3)3 can be treated with some success by inhalation of ZnDTPA . The main advantage of this method of treatment is that it can be self-administered very soon after an accidental intake, and it is effective for reducing the lung content of Am at doses about 10 times less than those usually used intravenously. Otherwise the efficacy of injected ZnDTPA is superior since in addition to removing 241Am from the lungs it can deplete appreciably the systemic deposit of the nuclide. There appears to be no advantage in using the lipophilic form of DTPA code-named Puchel , since following the inhalation or injection of the compound decorporation is not significantly increased relative to ZnDTPA .

The suitability of different preparations of thermoluminescent lithium borate for medical dosimetry.

The thermoluminescence properties of three different preparations of lithium borate have been studied with specific reference to their use in medical dosimetry. The properties of lithium borate powder doped with copper make it more attractive for low dose measurements than the more conventional phosphor doped with manganese. However, the energy response of the copper-doped material was not quite so suitable as that of the manganese-doped material for measuring doses to tissue at photon energies below 100 keV. It also exhibited appreciable light induced fading.