Hydrogen-rich water attenuates the radiotoxicity induced by tritium exposure in vitro and in vivo.

Radionuclide tritium is widely used in the nuclear energy production industry and creates a threat to human health through radiation exposure. Herein, the radioactive elimination and radioprotective effect of hydrogen-rich water (HRW), a potential antioxidant with various medical applications, on tritiated water (HTO) exposure, was studied in vitro and in vivo. Results showed that intragastric administration of HRW effectively promoted the elimination of urinary tritium, decreased the level of serum tritium and tissue-bound tritium (OBT), and attenuated the genetic damage of blood cells in mice exposed to HTO (18.5 MBq/kg). Pretreatment with HRW effectively reduces tritium accumulation in HTO-treated human blood B lymphocyte AHH-1 cells. In addition, the anti-oxidative properties of HRW could attenuate the increased intracellular ROS (such as O2•-, •OH and ONOO-), resulting in reversing the exhaustion of cellular endogenous antioxidants (reduced GSH and SOD), decreasing lipid peroxidation (MDA), relieving DNA oxidative damage, and depressing cell apoptosis and cytotoxicity induced by HTO exposure. In conclusion, HRW is expected to be an effective radioactive elimination agent through the competition effect of isotope exchange or a radioprotective agent by scavenging free radicals induced by HTO exposure.

Bone seeking labels as markers for bone turnover: effect of dosing schedule on labeling various bone sites in rats.

Urinary excretion of bone labels can be used to monitor bone resorption. Here we investigate the effects of dosing frequency on label incorporation of various sites when bone turnover was perturbed by ovariectomy. We compared tritiated tetracycline ((3)H-TC) and (45)Ca in two studies. Nine-month-old rats were given single or multiple injections of (3)H-TC and (45)Ca and sacrificed after 7 or 14 days. Six-month-old OVX rats were given (3)H-TC and (41)Ca tracers 1 or 3 months following ovariectomy (OVX + 1 mo or OVX + 3 mo, when bone turnover was higher or lower, respectively) and sacrificed 1 week, 1 month, 3 months, or 6 months postdose. Twenty-four-hour urine pools over 2-4 consecutive days as well as the proximal tibia, femur midshaft, lumbar vertebrae (L1-L4), and remaining skeleton were analyzed for (3)H, (45)Ca, and calcium content. Bone turnover as assessed by urinary (3)H-TC was greater in OVX + 1 mo compared to OVX + 3 mo rats up to 6 months postdose. (45)Ca labeling efficiency (% dose/g Ca) was significantly higher than for (3)H and labeling was higher in trabecular-rich than cortical-rich bone. This study affirms that a single administration of either (3)H-TC or (45)Ca is a useful approach to measuring bone turnover directly. The amount of label incorporation into bone was greater in bone sites that were more metabolically active and in all sites when closer vs farther from OVX.

Screening methods for estimating tritium dose.

Tritium intake may occur in certain workplaces by design or by accident. If the health physics staff has developed a formal bioassay program, then it is likely that dose estimates from tritium intake are readily determinable. However, in the case of tritium intake at a facility where no formal program exists, it may be necessary to make simple confirmatory estimates of dose due to tritium exposure. Lifetime dose estimates may be calculated by using data from urine samples taken over a period of time. If urine data are unavailable, estimates of committed dose equivalent may be made with air sample data and knowledge of workplace activities.

Tritium in the urine in Finnish people.

Tritium in urine was analysed from 227 randomly selected Finnish adults. The people were 18 to 65 of age. Urine samples were collected over night. The mean activity concentration of tritiated water in urine was 2.5 Bq l(-1) and the maximum activity concentration 18.3 Bq l(-1). The minimum detectable activity varied from 1.5 to 2.3 Bq l(-1). Because organically bound tritium is approximately 10% of the total tritium, its concentration was below the detection limit and could be ignored. The mean effective dose for Finnish people from tritium was 2.4 x 10(-3) microSv y(-1).

Internal dose assessments: uncertainty studies and update of ideas guidelines and databases within CONRAD project.

The work of Task Group 5.1 (uncertainty studies and revision of IDEAS guidelines) and Task Group 5.5 (update of IDEAS databases) of the CONRAD project is described. Scattering factor (SF) values (i.e. measurement uncertainties) have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Based upon this work and other published values, default SF values are suggested. Uncertainty studies have been carried out using both a Bayesian approach as well as a frequentist (classical) approach. The IDEAS guidelines have been revised in areas relating to the evaluation of an effective AMAD, guidance is given on evaluating wound cases with the NCRP wound model and suggestions made on the number and type of measurements required for dose assessment.

Buprenorphine duration of action: mu-opioid receptor availability and pharmacokinetic and behavioral indices.

BACKGROUND: Buprenorphine (BUP) is effective in the treatment of opioid dependence when given on alternating days, probably as a result of long-lasting occupation of micro opioid receptors (microORs). This study examined the duration of action of BUP at microORs and correlations with pharmacokinetic and pharmacodynamic outcomes in 10 heroin-dependent volunteers. METHODS: Availability of microOR (measured with positron emission tomography and [(11)C]-carfentanil), plasma BUP concentration, opioid withdrawal symptoms, and blockade of hydromorphone (HYD; heroin-like agonist) effects were measured at 4, 28, 52, and 76 hours after omitting the 16 mg/d dose of BUP in a study reported elsewhere. RESULTS: Relative to heroin-dependent volunteers maintained on BUP placebo, whole-brain microOR availability was 30%, 54%, 67%, and 82% at 4, 28, 52, and 76 hours after BUP. Regions of interest showed similar effects. Plasma concentrations of BUP were time dependent, as were withdrawal symptoms, carbon dioxide sensitivity and extent of HYD blockade. Availability of microOR was also correlated with BUP plasma concentration, withdrawal symptoms, and HYD blockade. CONCLUSIONS: Together with our previous findings, it appears that microOR availability predicts changes in pharmacokinetic and pharmacodynamic measures and that about 50%-60% BUP occupancy is required for adequate withdrawal symptom suppression (in the absence of other opioids) and HYD blockade.

An improved method for Organic Bound Tritium (OBT) determination in urine samples.

The Organic Bound Tritium (OBT) amount in the body may induce changes in the evaluation of the internal exposure to tritium, due to its different retention time relative to HTO. OBT measurements for urine are not performed routinely, mainly because of the lengthy work needed in preparation of the samples, when using the standard oxygen combustion method. A simpler and more rapid method based on liquid scintillation counting (LSC) was employed, and an evaluation was performed to check its suitability for urine samples. The principle of the proposed method is based on subtracting the LSC counts of the water phase sample (HTO) from the total activity of the urine sample (OBT+HTO). A good correlation was found between the results obtained when applying the proposed direct method and the Gold standard method. The minimum detectable activity when using this method was determined.

The in vivo degradation, absorption and excretion of PCL-based implant.

The in vivo degradation of poly (epsilon-caprolactone)(PCL) was observed for 3 years in rats. The distribution, absorption and excretion of PCL were traced in rats by radioactive labeling. The results showed that PCL capsules with initial molecular weight (Mw) of 66000 remained intact in shape during 2-year implantation. It broke into low molecular weight (Mw=8000) pieces at the end of 30 months. The Mw of PCL deceased with time and followed a linear relationship between logMw and time. Tritium-labeled PCL (Mw 3000) was subcutaneous implanted in rats to investigate its absorption and excretion. The radioactive tracer was first detected in plasma 15 days after implantation. At the same time radioactive excreta was recovered from feces and urine. An accumulative 92% of the implanted radioactive tracer was excreted from feces and urine by 135 days after implantation. In the mean while, the plasma radioactivity dropped to the background level. Radioactivity in the organs was all close to the background level confirming that the material did not cumulate in body tissue and could be completely excreted.

The uptake, excretion, and radiation hazards of tritiated thymidine in humans.

Nine patients with malignant disease were given i.v. injections of tritiated thymidine, 0.2 mCi/kg, for tumor cell kinetics studies. Serial plasma, urine, saliva, and air vapor samples were collected variously for up to 79 days, and tritium activity was measured. The initial half-life of plasma activity was rapid. After 1 day, the activity decayed with a half-life of 10.8 days, indicating equilibration of activity with the total body water. Urine activity was over 100 times the plasma activity within 1 hr, with equilibration approaching the plasma activity after 2 days, and then decayed at a similar rate. Saliva and air vapor activity increased to plasma levels and then decayed at the same rate as did plasma activity. In the first 24 hr, approximately one-third of the total injected activity was excreted in the urine. During the first 12 days there were 54.2% urinary and 10.6% insensible losses. Maximum losses determined by extrapolation of observed data were 68% urinary and 19.5% insensible losses, or a total of 87.5%. Approximately 7% of the injected activity may represent material initially incorporated into DNA but later metabolized and excreted. The radiation dose from total body water is estimated at 0.69 rad. The estimated dose absorbed by cell nuclei from incorporated material is a maximum of 20.5 rads. These radiation doses would not seem to contraindicate injection of 0.2 mCi tritiated thymidine per kg to patients in this clinical and experimental setting. Measurements of activity in personnel and room air indicate that the use of such doses is not hazardous if appropriate precautions are followed.

Quantitating isotopic molecular labels with accelerator mass spectrometry.

Accelerator mass spectrometry (AMS) traces isotopically labeled biochemicals and provides significant new directions for understanding molecular kinetics and dynamics in biological systems. AMS traces low-abundance radioisotopes for high specificity but detects them with MS for high sensitivity. AMS reduces radiation exposure doses to levels safe for use in human volunteers of all ages. Total radiation exposures are equivalent to those obtained in very short airplane flights, a commonly accepted radiation risk. Waste products seldom reach the Nuclear Regulatory Commission (NRC) definition of radioactive waste material for (14)C and (3)H. Attomoles of labeled compounds are quantified in milligram-sized samples, such as 20 microl of blood. AMS is available from several facilities that offer services and new spectrometers that are affordable. Detailed examples of designing AMS studies are provided, and the methods of analyzing AMS data are outlined.

The effect of a simultaneous dietary administration of xylitol and ethanol on bone resorption.

Our previous studies have shown that dietary xylitol supplementation diminishes bone resorption in rats, as well as protects against ovariectomy-induced increase of bone resorption during experimental osteoporosis. Interestingly, ethanol, when given simultaneously with xylitol, is known to increase blood concentration of xylitol. On the other hand, ethanol, when given alone, has been shown to increase bone resorption. The aim of the present study was to evaluate the effects of a simultaneous dietary administration of 10% xylitol and 10% ethanol on bone resorption. Bone resorption was determined using measurement of urinary excretion of hydrogen 3 (3H) radioactivity in 3H-tetracycline prelabeled rats. Already 4 days after the beginning of dietary supplementations, excretion of 3H was about 15% lower in the xylitol group (diet supplemented with 10% xylitol) and about 25% lower in the xylitol-ethanol group (diet supplemented with 10% xylitol and 10% ethanol) as compared to the controls. The excretion of 3H in these groups remained smaller than that of the controls throughout the entire study period of 40 days. The excretion of 3 H in the xylitol-ethanol group remained also smaller than that of the xylitol group. Bone mineral density and bone mineral content were determined with a peripheral quantitative computed tomography (pQCT) system from the rat tibiae at the end of the experiment. Trabecular bone mineral density and trabecular bone mineral content were significantly greater in the xylitol group and in the xylitol-ethanol group compared to the controls. They were also greater in the xylitol-ethanol group as compared to the xylitol group. Cortical bone mineral density and cortical bone mineral content did not differ significantly between the groups. In conclusion, a simultaneous dietary supplementation with 10% xylitol and 10% ethanol seems to diminish bone resorption and to increase trabecular bone mineral density and trabecular bone mineral content in rats. These effects seem to be stronger than the effects induced by 10% xylitol supplementation alone.

Determination of total tritium in urine from residents living in the vicinity of nuclear power plants in Qinshan, China.

To estimate the tritium doses of the residents living in the vicinity of a nuclear power plant, urine samples of 34 adults were collected from residents living near the Qinshan nuclear power plant. The tritium-in-urine (HTO plus OBT) was measured by liquid scintillation counting. The doses of tritium-in-urine from participants living at 2, 10 and 22 km were in a range of 1.26-6.73 Bq/L, 1.31-3.09 Bq/L and 2.21-3.81 Bq/L, respectively, while the average activity concentrations of participants from the three groups were 3.53 ± 1.62, 2.09 ± 0.62 and 2.97 ± 0.78 Bq/L, respectively. The personal committed effective doses for males were 2.5 ± 1.7 nSv and for females they were 2.9 ± 1.3 nSv. These results indicate that tritium concentrations in urine samples from residents living at 2 km from a nuclear power plant are significantly higher than those at 10 km. It may be the downwind direction that caused a higher dose in participants living at 22 km. All the measured doses of tritium-in-urine are in a background level range.

Determination of tritium concentrations in humans before the development of a nuclear power plant in Turkey.

The most widely used method to determine the level of tritium in humans is testing urine. Tritium concentrations in urine samples of 100 persons aged 18-66 years selected randomly from a pilot region in Turkey were analysed. The average activity concentration of urine samples was 4.66 ± 1.94 Bq L(-1) and the maximum activity concentration was 27.91 Bq L(-1). The minimum detectable activity was 2.38 Bq L(-1). The annual effective dose from tritium was also evaluated on the basis of the measurement results and reference values recommended by the International Commission on Radiological Protection. The effective doses for males and females were 4.56 and 3.54 nSv, respectively. These results were lower than the permissible annual effective dose for members of the public.

Validation of a metabolic model for tritium.

The purpose of this paper is to validate a metabolic model describing the kinetics of tritium in man. The validation is based on measurements of background levels of loose and bound tritium in Italian subjects and their diets. Model predictions are compared with empirical measurements of tritium in human urine and tissue samples, and appear to be in close agreement.

Comparative biokinetics of tritium in rats during continuous ingestion of tritiated water and tritium-labeled food.

PURPOSE: The biokinetics of tritium during continuous ingestion of tritiated water and tritiated wheat were investigated to estimate the radiation dose rates at the end of two modes of chronic exposure. MATERIALS AND METHODS: Wistar strain male rats continuously ingested tritiated water as drinking water and tritiated wheat as food for 14 weeks. Urine and tissue samples were obtained and total tritium in the fresh wet samples and organically bound tritium (OBT) in the freeze-dried samples were determined. RESULTS: The biokinetics of tritium was different between the two modes of exposure. The concentration of total tritium in the tissues exposed to tritiated water attained a steady-state condition by 2-3 weeks. The steady-state condition in the case of exposure to tritiated wheat was not observed for 10 weeks after the start of exposure in the majority of tissues. The relatively efficient and prolonged OBT formation during chronic exposure to tritiated wheat resulted in relatively high incorporation and retention of tritium in the tissues compared with those for exposure to the same activity of tritiated water. CONCLUSION: Radiation dose rates estimated at the end of continuous ingestion showed that tritiated wheat gave higher dose rates than tritiated water by a factor of 1.3 to 4.5, but the factors were within 2.0 in the majority of tissues except for small intestine and adipose tissue.

Assessing the plasma pharmacokinetics, tissue distribution, excretion and effects on cholesterol pharmacokinetics of a novel hydrophilic compound, FM-VP4, following administration to rats.

PURPOSE: The purpose of this project was to 1) assess the disposition kinetics of [3H]-cholesterol following co-administration with a novel hydrophilic compound, FM-VP4, and 2) determine the pharmacokinetics, tissue distribution and excretion of [3H]FM-VP4 following single oral (150 mg/kg which includes 100 mCi of radiolabel) and intravenous (15 mg/kg which includes 10 mCi of radiolabel) doses. METHODS: Following an overnight fast (12-16 h) and 48 h post-surgery, adult male Sprague Dawley rats were divided into six treatment groups (n=4/group). Groups received single oral doses of 25 mCi/ml [3H]cholesterol alone or with 5, 10, 20, 50 and 100 mg/kg FM-VP4 at 0700 h. Ten percent Intralipid was used to solubilize and co-administer [3H]-cholesterol and FM-VP4. LC-MS analysis confirmed minimal cholesterol and vegetable stanol content within 10% Intralipid. Thin layer chromatography was used to confirm that the majority of radioactivity measured in plasma was associated with either esterified or unesterified cholesterol. In a second study pharmacokinetics of [3H]FM-VP4 were studied following intravenous or orally gavaged doses (n=8). Tissues, urine and feces were also collected in FM-VP4 kinetics study to measure tissue distribution of radioactivity. Plasma [3H]-cholesterol and [3H]FM-VP4 were tested for radioactivity. RESULTS: FM-VP4 co-administration significantly decreased [3H]-cholesterol AUC0-48h and Cmax, and increased CL/F and Vd/F of [3H]-cholesterol as compared to controls in a dose-dependent manner. Following oral administration of [3H]FM-VP4, the majority of radioactivity following was recovered in the feces and gastrointestinal (GI) tract. The compound exhibited an oral bioavailability of 6.5%. Following IV administration, a two-compartment pharmacokinetic model was observed and the majority of the radioactivity was recovered in the GI tract. CONCLUSIONS: FM-VP4 reduces plasma concentration of [3H]-cholesterol in fasting rats. [3H]FM-VP4 has a very low oral bioavailability.

Regulation of renal tubular bile acid transport in the early phase of an obstructive cholestasis in the rat.

BACKGROUND/AIMS: In obstructive liver diseases, urinary excretion of bile acids is markedly enhanced. The mechanism of this effect is not entirely clear. The aim of the present study was to assess the glomerular and tubular factors involved in the renal handling of bile acids during the early phase of an obstructive cholestasis induced by a 24-hour bile duct ligation in rats. METHODS: In addition to conventional clearance experiments, taurocholate transport was studied on proximal tubular cells freshly isolated from rat kidneys. The expression of the taurocholate transport protein was determined in these cells by immunoblotting. RESULTS: Glomerular filtration rate and arterial blood pressure were not significantly affected by the cholestasis induced. The (3)H-taurocholate and (3)H-cholate clearances significantly increased whereas the fractional tubular reabsorption rates of these bile acids significantly fell. Probenecid did not affect the (3)H-taurocholate and (3)H-cholate clearances. By employing S0960, a specific inhibitor of the sodium-dependent bile salt transporter ASBT, it could be shown that this transporter mediates (3)H-taurocholate uptake into the proximal tubular cells. The bile duct ligation caused a significant decrease of the V(max) value of the taurocholate transporter indicating a downregulation of this transporter in cholestasis. The downregulation occurred without a change of the ASBT protein content of the proximal tubular cells. CONCLUSION: The results demonstrate that there is a functional adaptive downregulation of renal tubular bile acid transport enhancing renal clearance of bile acids during the early phase of an obstructive cholestasis.

Radiotoxicological intercomparisons organised by the Commissariat à l'Energie Atomique group in France.

People working in French nuclear plants are monitored either by whole body counting or by the measurement of biological samples. The radiochemical and radiometric procedures used have to be periodically reviewed. A working group, including practising biologists from CEA, EDF and the Armed Forces Health Service, instituted comparisons of radiotoxicological test assessments. Since 1978, about 60 intercomparisons have been made. Currently 30 European laboratories are involved in these intercomparisons. This paper provides a brief history of the intercomparison exercises, describes the logistics of sample collection and preparation, and presents the results, showing the position of each laboratory in relation to the reference and median values. Diagrams produced by radiochemical analysis, relating to plutonium in urine and in faecal samples, and to tritium, strontium and enriched uranium in urine, are analysed.

A unique method of determining 3H intakes as a fraction of the annual limit of intake.

The internal dose due to 3H is generally estimated by the measurement of average 3H concentration in urine. The concentration in urine, however, depends very much on the effective half-life which in turn varies from season to season and from person to person. This means that the annual limit of intake (ALI) would also vary. The latest recommendations of International Commission on Radiological Protection (ICRP) suggest that internal dose be controlled as fractions of ALI. This paper suggests a method for determining intake as a fraction of the ALI by measuring 3H concentrations in urine and inter alia taking into account the variations of effective half-life in individuals.

Skin-contact exposure to tritium-gas-contaminated stainless-steel surfaces.

One of the radiation protection problems potentially encountered in tritium-handling facilities is contamination of metal surfaces. Experiments with hairless rats have demonstrated that when intact skin is brought into contact with tritium-gas-contaminated stainless-steel surfaces, tritium can be fixed as organically bound tritium (OBT) and as tritiated oxide (HTO) in the skin. The radiological hazard associated with this route of tritium uptake is determined by the retention and distribution of tritium in the skin and other organs. The experimental data suggest that the OBT in the skin serves as an input source to the rest of the body. The urinary excretion of tritium shows a biphasic excretion for OBT and a single-phase clearance for HTO from the body. The results indicate that the exposure from this mode of contamination results in long retention of tritium in the skin as well as in non-uniform distribution of tritium in organs and macromolecules. This information is useful in evaluating the possible dosimetric concerns from this mode of exposure.