Heather Wyatt

Low-Dose Radiation Exposure and Atherosclerosis in ApoE−/− Mice

Abstract The hypothesis that single low-dose exposures (0.025–0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE−/−). Mice were exposed either at an early stage of disease (2 months of age) and examined 3 or 6 months later or at a late stage of disease (8 months of age) and examined 2 or 4 months later. Changes in aortic lesion frequency, size and severity as well as total serum cholesterol levels and the uptake of lesion lipids by lesion-associated macrophages were assessed. Statistically significant changes in each of these measures were observed, depending on dose, dose rate and disease stage. In all cases, the results were distinctly non-linear with dose, with maximum effects tending to occur at 25 or 50 mGy. In general, low doses given at low dose rate during either early- or late-stage disease were protective, slowing the progression of the disease by one or more of these measures. Most effects appeared and persisted for months after the single exposures, but some were ultimately transitory. In contrast to exposure at low dose rate, high-dose-rate exposure during early-stage disease produced both protective and detrimental effects, suggesting that low doses may influence this disease by more than one mechanism and that dose rate is an important parameter. These results contrast with the known, generally detrimental effects of high doses on the progression of this disease in the same mice and in humans, suggesting that a linear extrapolation of the known increased risk from high doses to low doses is not appropriate.

A radiation-induced adaptive response prolongs the survival of prion-infected mice.

Previously, it has been demonstrated that an adaptive response that includes the prevention, repair, and removal of oxidative damage can be evoked by radiation at dose rates substantially lower than those at which risks have been observed. The exact pathogenic mechanism of prion diseases is unknown, but circumstantial evidence suggests that oxidative stress plays a central role. Exposure of prion-infected mice to four 500 mGy/fraction doses of (60)Co γ-radiation administered every other day at a low dose rate (0.5 mGy/min) starting at 2 days before infection, 7 days postinfection (dpi), or 50 dpi significantly prolonged the survival of infected mice. The 500-mGy radiation treatments started at 50 dpi also significantly prolonged the symptom-free period of the disease and caused a significant delay in the rise of the 8-hydroxydeoxyguanosine concentration observed in the urine of nonirradiated infected mice at 98 dpi. The duration of the reduction in oxidative stress achieved by the radiation treatments was similar in length to the prolonged survival of the irradiated mice. This suggests that the adaptive response induced by low-dose whole-body radiation treatments prolongs the survival of prion-infected mice by reducing oxidative stress.

Metabolism of 210Po in rats: volatile 210Po in excreta

Polonium-210 ((210)Po) is one of the most toxic radionuclides and was used as a poison in the Alexander Litvinenko case. In this study of the metabolism of (210)Po in rats, volatile (210)Po in excreta was measured, filling a knowledge gap of the previous studies. Five rats were intravenously administrated with 2 kBq and another five with 10 kBq of (210)Po (citrate form). They were housed in a glass Metabowl system for 4 d following the administration. Volatile (210)Po from the excreta was collected in a trapping system filled with liquid scintillation cocktail and was measured by liquid scintillation counting. Results showed that the daily excretion of volatile (210)Po by the rats is in a very small percentage (0.002-0.009 %) of the administered amounts. However, if the administered amount is large, the excretion of volatile (210)Po can be significant.

Tritium ( 3 H) Retention In Mice: Administered As HTO, DTO or as 3 H-Labeled Amino-Acids

Abstract The objective of this study was to compare the biokinetics of injected 3H-labeled light (HTO) and heavy (DTO) water in CBA/CaJ mice and to compare the organ distribution and/or body content of 3H administered by chronic ingestion for 1 mo to C57Bl/6J mice, as either 3H-labeled water or 3H-labeled amino acids (glycine, alanine and proline). HTO and DTO were administered to CBA/CaJ mice by single intraperitoneal injection and body retention was determined for up to 384 h post-injection. Tritium-labeled water or 3H-labeled amino acids were given to C57Bl/6J mice ad libitum for 30 d in drinking water. Body content and organ distribution of 3H during the period of administration and subsequent to administration was determined by liquid scintillation counting. No differences were found between the biokinetics of HTO and DTO, indicating that data generated using HTO can be used to help assess the consequences of 3H releases from heavy water reactors. The results for 3H-water showed that the concentration of radionuclide in the mice reached a peak after about 10 d and dropped rapidly after the cessation of 3H administration. The maximum concentration reached was only 50% of that in the water consumed, indicating that mice receive a significant fraction of their water from respiration. Contrary to the findings of others, the pattern of 3H retention following the administration of a cocktail of the labeled amino acids was very little different from that found for the water. This is consistent with the suggestion that most of the ingested amino acids were rapidly metabolized, releasing water and carbon dioxide.

Environmentally Relevant Chronic Low-Dose Tritium and Gamma Exposures do not Increase Somatic Intrachromosomal Recombination in pKZ1 Mouse Spleen.

The toxicity of tritium is a public health concern given its presence and mobility in the environment. For risk predictions using radiological protection models, it is essential to allocate an appropriate radiation weighting factor (WR). This in turn should be consistent with the observed relative biological effectiveness (RBE) of tritium beta radiation. Although the International Commission on Radiological Protection (ICRP) currently recommends a WR of 1 for the calculation of committed effective dose for X rays, gamma rays and electrons of all energies, including tritium energies, there are concerns that tritium health risks are underestimated and that current regulatory tritium drinking water standards need revision. In this study, we investigated potential cytotoxic and genotoxic effects in mouse spleen after one month and eight months of chronic exposure to low-dose tritiated water (HTO). The dose regimes studied were designed to mimic human chronic consumption of HTO at levels of 10 kBq/l, 1 MBq/l and 20 MBq/l. The total doses from these radiation exposures ranged from 0.01 to 180 mGy. We also compared the biological effects of exposure to HTO with equivalent exposure to external whole-body 60Co gamma rays. Changes in spleen weight and somatic intrachromosomal recombination (DNA inversions) in spleen tissue of pKZ1Tg/+ mice were monitored. Our results showed no overall changes in either spleen organ weights and no increase mouse splenic intrachromosomal recombination frequencies, indicating that current drinking water standards for tritium exposure in the form of HTO are likely to be adequately protective against cytotoxic and genotoxic damage in spleen. These results demonstrate no evidence for cytotoxicity or genotoxicity in mouse spleen following chronic exposures to HTO activities (or equivalent gamma doses) up to 20 MBq/L.

Correction: Low-Dose Irradiation Affects Expression of Inflammatory Markers in the Heart of ApoE -/- Mice.

[This corrects the article DOI: 10.1371/journal.pone.0119661.].

Is alpha spectrometry reliable for 210Po urine bioassay

Typically the bioassay method for (210)Po in urine by alpha spectrometry (AS) involves wet decomposition of the sample, which may cause a loss of (210)Po if volatile species are present. To test this hypothesis, urine samples collected from two rats that were i.v. administered with polonium citrate were measured by both AS and liquid scintillation counting, where urine samples were mixed with a scintillation cocktail without any treatment. A split-plot design method was used to compare results from the two measurement methods, showing no evidence of a difference between the two methods. This suggests that the AS method is reliable for (210)Po urine bioassay.

Metabolism of 210Po in rats: volatile 210Po from faeces.

The metabolic formation of volatile (210)Po species in a rat that was intravenously administered with (210)Po-citrate was investigated in this study. A slurry of the faecal sample was prepared in water and was bubbled with nitrogen gas in a closed system. The discharged gas was passed through a trapping device filled with liquid scintillation cocktail in order to capture any volatile (210)Po species. The amount of (210)Po trapped in the scintillation cocktail was measured by a liquid scintillation analyser that provided evidence of the presence of volatile (210)Po species in the faeces. The presence of volatile (210)Po in the faeces indicates that the metabolic formation of volatile (210)Po is likely to occur in the gut due to bacterial activity. The amount of volatile (210)Po species was compared with the daily faecal excretion of (210)Po. After 2 h of bubbling, the volatile (210)Po collected from the faeces sample was found to be between 1.0 and 1.7 % of the daily faecal excretion for the 4 d following (210)Po-citrate administration.

Biokinetics of 210Po in rats: excretion via urine and faeces and retention in tissues and organs

Daily excretions of ²¹⁰Po from rats via urine and faeces following i.v. administration of polonium citrate, from Day 2 to Day 5, were reported, together with retentions in tissues and organs on Day 5. Emphasis is given to the methods of measurement and data quality rather than to the discussion of the observations. The authors aim to contribute data for developing or refining the biokinetic model for ²¹⁰Po metabolism.

Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation

The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal β-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 – 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo, the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed.