[Polonium-210 acute and chronic pathomorphology and pathogenesis].

In the present review, the data on the pathology of acute and chronic polonium injuries available from the an open-access domestic and foreign literature are primarily systemized and analyzed. The historical background of the research is presented in brief. On the basis of clinical and experimental generalizations, the current concept regarding the pathogenesis of polonium intoxication has been developed.

[The death of Yasser Arafat: molecular-genetic authentication of the remains as an indispensable condition for the evaluation of the medical hypotheses of the cause of his death].

The objective of the present study was the molecular-genetic authentication of the remains as an indispensable condition for the evaluation of the medical hypotheses of the cause of death in 2004 of Yasser Arafat, the former Palestinian leader and the first president of the Palestinian National Administration, the Nobel Peace Prize laureate. We carried out molecular-genetic investigations aimed at establishing the circumstances and cause of the death of Yasser Arafat including the analysis of the relevant medical documentation, the examination of the burial place at Ramallah, remains, and personal belongings stored in his Al Muqata'ah residence at Ramallah. The objective of the present molecular- genetic investigations was to confirm the authenticity of the fragments of Yasser Arafat's remains available for radio-toxicological, chemical toxicological, and other laboratory studies. The reference objects were the contact traces left on the personal belongings by their owner. The aggregate probabilistic estimate of the coincidence of genotype traits of autosomal DNA, Y-chromosomal DNA, and mtDNA was at least 99,(9)29 4% which gives evidence of the genetic identity of the objects of study. It is this value (99.999999 <...> 9999999(29) 4%) that characterizes the probability that the bone fragments provided for the laboratory studies are actually authentic remains of Yasser Arafat.

Review of chemical and radiotoxicological properties of polonium for internal contamination purposes.

The discovery of polonium (Po) was first published in July, 1898 by P. Curie and M. Curie. It was the first element to be discovered by the radiochemical method. Polonium can be considered as a famous but neglected element: only a few studies of polonium chemistry have been published, mostly between 1950 and 1990. The recent (2006) event in which (210)Po evidently was used as a poison to kill A. Litvinenko has raised new interest in polonium. 2011 being the 100th anniversary of the Marie Curie Nobel Prize in Chemistry, the aim of this review is to look at the several aspects of polonium linked to its chemical properties and its radiotoxicity, including (i) its radiochemistry and interaction with matter; (ii) its main sources and uses; (iii) its physicochemical properties; (iv) its main analytical methods; (v) its background exposure risk in water, food, and other environmental media; (vi) its biokinetics and distribution following inhalation, ingestion, and wound contamination; (vii) its dosimetry; and (viii) treatments available (decorporation) in case of internal contamination.

Health Risk of Polonium 210 Ingestion via Drinking Water: An Experience of Malaysia.

The presence of toxic polonium-210 (Po-210) in the environment is due to the decay of primordial uranium-238. Meanwhile, several studies have reported elevated Po-210 radioactivity in the rivers around the world due to both natural and anthropogenic factors. However, the primary source of Po-210 in Langat River, Malaysia might be the natural weathering of granite rock along with mining, agriculture and industrial activities. Hence, this is the first study to determine the Po-210 activity in the drinking water supply chain in the Langat River Basin to simultaneously predict the human health risks of Po-210 ingestion. Therefore, water samples were collected in 2015⁻2016 from the four stages of the water supply chain to analyze by Alpha Spectrometry. Determined Po-210 activity, along with the influence of environmental parameters such as time-series rainfall, flood incidents and water flow data (2005⁻2015), was well within the maximum limit for drinking water quality standard proposed by the Ministry of Health Malaysia and World Health Organization. Moreover, the annual effective dose of Po-210 ingestion via drinking water supply chain indicates an acceptable carcinogenic risk for the populations in the Langat Basin at 95% confidence level; however, the estimated annual effective dose at the basin is higher than in many countries. Although several studies assume the carcinogenic risk of Po-210 ingestion to humans for a long time even at low activity, however, there is no significant causal study which links Po-210 ingestion via drinking water and cancer risk of the human. Since the conventional coagulation method is unable to remove Po-210 entirely from the treated water, introducing a two-layer water filtration system at the basin can be useful to achieve SDG target 6.1 of achieving safe drinking water supplies well before 2030, which might also be significant for other countries.

Bioaccumulation of polonium 210Po in marine birds.

The aim of this work was to determine the 210Po content in marine birds which permanently or temporally live in the Polish part of the Baltic Sea. We chose 11 species of sea birds: three species permanently residing at southern Baltic Sea, four species of wintering birds and three species of migrating birds. The results show that the polonium is non-uniformly distributed in the marine birds. The highest activities of 210Po were observed in feathers, muscles and liver and the lowest in skin and skeleton. Species of birds that eat crustaceans, molluscs, fish and plants (long-tailed duck Clangula hyemalis, white-winged scoter Melanitta fusca) accumulated more polonium than species that eat mainly fish (great cormorant Phalacrocorax carbo, common guillemot Uria aalge) or plants (tufted duck Aythya fuligula). Moreover, about 63% of the 210Po that was located in feathers of razorbil (Alca torda) and long-tailed duck (C. hyemalis) was apparently adsorbed, suggesting an external source such as the air. It means that the adsorption of 210Po on the feather surface may be an important transfer from air to water.

Association between radionuclides (210Po and 210Pb) and antioxidant enzymes in oak (Quercus coccifera) and mastic tree (Pistacia lentiscus).

The activity levels of naturally occurring radionuclides Polonium-210 and lead-210 in different subjects including plant species have direct or indirect impact on human beings. High levels of ionising radiation cause oxidative stress and the interaction between antioxidative defense and radionuclides is not well established in plant systems. In this study, we aimed to understand the impact of oxidative stress caused by 210Po and 210Pb in two Mediterranean plants; Quercus coccifera and Pistacia lentiscus. We analysed the constitutive and seasonal levels of 210Po, 210Pb, lipid peroxidation levels, superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities in the field-collected samples. The highest activity concentrations of 210Po and 210Pb were detected in both plants in summer and Q. coccifera had higher levels than that of P. lentiscus. SOD and APX activity trends were different between oak and mastic; as compared to P. lentiscus, Q. coccifera efficiently used the two major components of antioxidative defense. Lipid peroxidation levels were low in both plants in all seasons except that of spring which were in good agreement with high antioxidant enzyme activities. In conclusion, we found that high 210Po and 210Pb activity concentrations in oak and mastic did not interfere with their growth and life cycles. The ability of both plants for survival and adaptation to Mediterranean environmental constraints provided an additional advantage for coping radionuclide induced oxidative stress as well.

Interactions between polonium-210 alpha-radiation, benzo(a)pyrene, and 0.9% NaCl solution instillations in the induction of experimental lung cancer.

Benzo(a)pyrene and 210Po were administered both simultaneously and sequentially by intratracheal instillations to Syrian golden hamsters in experiments designed to identify any synergistic interactions between these carcinogens. Their effects were additive after simultaneous administration. A significant synergistic interaction between the two agents appeared to occur when benzo(a)pyrene exposure followed 4 months after 210Po exposure. Most of this effect could be ascribed, however, to a potentiating effect of subsequent 0.9% NaCl solution instillations on 210Po carcinogenesis. These results emphasize the fact that seemingly innocuous stimuli may significantly potentiate lung carcinogenesis. The implications of these findings in terms of the interactions between alpha-radiation and cigarette smoke in human populations are discussed.

Serial sacrifice study of pathogenesis of 210Po-induced lung tumors in Syrian golden hamsters.

The pathogenesis of 210Po-induced tumors in the peripheral lung of Syrian golden hamsters has been studied in a serial sacrifice experiment utilizing both plastic (glycol methacrylate) and routine paraffin embedding procedures for lung sections. A rapid progression from hyperplasia of bronchiolar-type cells that appear in the alveolar region to malignant tumors was documented. Tumors began appearing as early as 15 weeks after the first intratracheal instillation of 210Po.

Proliferative and morphological changes in the pulmonary epithelium of the Syrian golden hamster during carcinogenesis initiated by 210Po alpha alpha-radiation.

The role of cellular proliferation in a two-stage model of carcinogenesis in the hamster lung was investigated. Syrian golden hamsters were treated intratracheally with either one instillation of 0.2 microCi of 210Po (Po-0 group), seven weekly instillations of BP (0-BP group), or 0.2 microCi 210Po followed 15 weeks later by either seven instillations of 0.9% NaCl solution (Po-Sal group) or seven instillations of BP (Po-BP group). All BP instillations were 3 mg each of BP:ferric oxide (1:1, w/w) carrier particles). Serial sacrifices were performed for up to 85 weeks. Two hr before sacrifice, each animal was given i.p. injections of 200 microCi of [3H]thymidine. Glycol methacrylate section autoradiographs (1 micrometer) were prepared. Labeling indices in the alveolar region, labeling of terminal bronchiolar cells, and morphological changes were examined. Equal numbers of Po-Sal and Po-BP animals developed lung tumors. No tumors were found in Po-0 or 0-BP animals. Tumor development was preceded by the appearance of hyperplastic areas of bronchiolar-type cells in the alveolar region and by changes in morphology of bronchiolar cells. Labeling indices in the alveolar region of the treated groups were slightly increased relative to untreated controls. Labeling of terminal bronchiolar cells was highest in the Po-BP and 0-BP groups and was associated with much inflammation. A single 0.9% NaCl solution instillation also increased proliferation of bronchiolar cells. We conclude that 0.9% NaCl solution instillations may potentiate carcinogenesis in the hamster lung by acting as a nonspecific stimulus to proliferation; in addition, we conclude that not all hyperplasia progresses on to form lung tumors in the Po-BP and Po-Sal groups.

(210)Po in drinking water, its potential health effects, and inadequacy of the gross alpha activity MCL.

Polonium-210 ((210)Po) is a naturally-occurring, carcinogenic member of the (238)U decay series and the granddaughter of (210)Pb. It has a half life of 138.4days and is rarely found in drinking water at levels exceeding 5mBq/L because it strongly binds to aquifer sediment. When the current US Maximum Contaminant Level (MCL) covering (210)Po was promulgated in December 2000, very little was known about its occurrence and the processes responsible for mobilizing it. More is now known about the processes that mobilize (210)Po from sediments and a review of recent occurrence data show that it may not be as rare in the US as the US Environmental Protection Agency (USEPA) thought in 2000. Worldwide, only about 2200 analyses for (210)Po in drinking water were identified, with activities exceeding 500mBq/L being found only in Finland, India, Sweden, and the US. The median of 400 (210)Po analyses from the US is 4.75mBq/L and >10% of the samples exceed 500mBq/L. Current compliance-monitoring regulations in the US essentially guarantee that (210)Po contamination will not be detected except in very contaminated wells. Major problems with the US Gross Alpha Activity MCL include the volatility of (210)Po and extended holding times and sample-compositing methods that can allow the majority of (210)Po in a sample bottle to decay before analysis. In light of new information, the radionuclide rule should be changed and direct measurements of (210)Po should be made in all public-water supply wells to rule out its presence. Much of the important biological and toxicological research on (210)Po is more than four decades old and new laboratory research using modern tools is needed. Biological and epidemiological investigations of known contaminated areas are needed to assess the effect (210)Po exposure is having on animals and humans consuming the water.

Effects of 210Po alpha particles on survival and preneoplastic transformation of primary rat tracheal epithelial cells irradiated while in suspension or in the intact tissue.

Rat tracheal epithelial cells exhibited exponential cell killing when exposed to 210Po alpha particles as single cell suspensions or in the intact tissue. Survival of cells in the intact tissue was not significantly different from that observed with cell suspensions. Comparison of survival of cells exposed in suspension to 300 kVpX rays yielded an RBE of 6.3. Measurements of basal cell nuclei were used to determine that a single traversal of a cell nucleus had a high probability of causing cell inactivation. This was also observed in mink lung cells and CHO cells exposed in an identical manner. There were no significant increases in frequencies of preneoplastic transformation observed for a range of exposures (0.0007 to 0.05 alpha particles/micron2). Examination of intact tracheal transplants which were irradiated with alpha particles also failed to reveal any preneoplastic or neoplastic changes.

Vitamins as radioprotectors in vivo. I. Protection by vitamin C against internal radionuclides in mouse testes: implications to the mechanism of damage caused by the Auger effect.

The potential of vitamin C, an antioxidant, to protect the radiosensitive spermatogonial cells in mouse testes against the effects of chronic irradiation by radionuclides incorporated into tissue was investigated. Interestingly, when injected intratesticularly, a small and nontoxic amount of vitamin C (1.5 microgram in 3 microliters saline) protected the spermatogonia against the damage associated with high-LET radiation caused by Auger electrons from similarly administered 5-(125I)-iodo-2'-deoxyuridine (125IdU). A dose modification factor (DMF) of 2.3 was obtained. In contrast, no protection was observed when 210Po, an alpha-particle emitter, was administered similarly. These findings suggest that the mechanism of action of the Auger effect is of an indirect nature, which is in contrast to the direct action generally believed to be responsible for biological damage caused by high-LET radiations.

Vitamins as radioprotectors in vivo. II. Protection by vitamin A and soybean oil against radiation damage caused by internal radionuclides.

Tissue-incorporated radionuclides impart radiation energy over extended periods of time depending on their effective half-lives. The capacity of vitamin A dissolved in soybean oil to protect against the biological effects caused by internal radionuclides is investigated. The radiochemicals examined are DNA-binding 125IdU, cytoplasmically localized H125IPDM and the alpha-particle emitter 210Po citrate. As in our previous studies, spermatogenesis in mice is used as the experimental model and spermatogonial cell survival is the biological end point. Surprisingly, soybean oil itself provides substantial and equal protection against the Auger effect of 125IdU, which is comparable to a high-LET radiation effect, as well as the low-LET effects of H125IPDM, the dose modification factors (DMFs) being 3.6 +/- 0.9 (SEM) and 3.4 +/- 0.9, respectively. The protection afforded by the oil against the effects of 5.3 MeV alpha particles emitted by 210Po is also significant (DMF = 2.2 +/- 0.4). The presence of vitamin A in the oil further enhanced the radioprotection against the effect of 125IdU (DMF = 4.8 +/- 1.3) and H125IPDM (DMF = 5.1 +/- 0.6); however, no enhancement is provided against the effects of alpha particles. These interesting results with soybean oil and vitamin A, together with data on the subcellular distribution of the protectors, provide clues regarding the mechanistic aspects of the protection. In addition, the data for vitamin A reaffirm our earlier conclusion that the mechanism by which DNA-bound Auger emitters impart biological damage is primarily indirect in nature.

Reduction of subacute lethal radiotoxicity of polonium-210 in rats by chelating agents.

The protective effect of N,N'-di(2-hydroxyethyl)ethylene-diamine-N,N'-biscarbodithioate (HOEtTTC) against the subacute lethal radiotoxicity of polonium-210 was investigated in a survival study and by histopathological and haematological examinations of some organs and tissues in Sprague-Dawley rats. This effect was compared with that of N,N'-diethylamine-N-carbodithioate (diethy dithiocarbamate, DDTC). In the survival study, rats injected in intravenously solely with a lethal amount of 210Po (1.45 MBq kg-1 body mass) died within 14-44 days while 90% of rats treated with HOEtTTC survived for 5 months until sacrificed. When treated with DDTC all rats died within 36-93 days. In the histopathological examination, relevant changes resulting from incorporation of 210Po were found in lymph nodes, thymus and humeral bone marrow. After the treatment with HOEtTTC no pathological changes were observed. In the haematological examination, severe reduction in blood and femoral bone marrow (BM) cell counts was revealed in rats injected with 210Po. This reduction was reversed by treatment with HOEtTTC. Treatment with DDTC led only to partial recovery of blood and BM cell count. In conclusion, under the conditions of the experiment only HOEtTTC was fully effective in reducing subacute lethal radiotoxicity of 210Po.

A systemic biokinetic model for polonium.

Although the biokinetics of polonium has been studied extensively, interpretation of the data is complicated by potential differences with species and route of exposure and the questionable reliability of much of the reported excretion data for man. A study was undertaken to identify the data that are most likely to represent the typical behavior of polonium and apply those data to construct an improved, physiologically realistic systemic biokinetic model for polonium in man. Such a model is needed for interpretation of urinary excretion data for workers exposed to 210Po and reconstruction of the radiation doses received by those workers. This paper reviews the database on the biokinetics of polonium and describes a new systemic biokinetic model for polonium in man.

Occurrence of ²¹°Po and biological effects of low-level exposure: the need for research.

BACKGROUND: Polonium-210 (²¹°Po) concentrations that exceed 1 Bq/L in drinking-water supplies have been reported from four widely separated U.S. states where exposure to it went unnoticed for decades. The radionuclide grandparents of ²¹°Po are common in sediments, and segments of the public may be chronically exposed to low levels of ²¹°Po in drinking water or in food products from animals raised in contaminated areas. OBJECTIVES: We summarized information on the environmental behavior, biokinetics, and toxicology of ²¹°Po and identified the need for future research. METHODS: Potential linkages between environmental exposure to ²¹°Po and human health effects were identified in a literature review. DISCUSSION: ²¹°Po accumulates in the ovaries where it kills primary oocytes at low doses. Because of its radiosensitivity and tendency to concentrate ²¹°Po, the ovary may be the critical organ in determining the lowest injurious dose for ²¹°Po. ²¹°Po also accumulates in the yolk sac of the embryo and in the fetal and placental tissues. Low-level exposure to ²¹°Po may have subtle, long-term biological effects because of its tropism towards reproductive and embryonic and fetal tissues where exposure to a single alpha particle may kill or damage critical cells. ²¹°Po is present in cigarettes and maternal smoking has several effects that appear consistent with the toxicology of ²¹°Po. CONCLUSIONS: Much of the important biological and toxicological research on ²¹°Po is more than four decades old. New research is needed to evaluate environmental exposure to ²¹°Po and the biological effects of low-dose exposure to it so that public health officials can develop appropriate mitigation measures where necessary.

(210)Po and (210)Pb activity concentrations in Mytilus galloprovincialis from Croatian Adriatic coast with the related dose assessment to the coastal population.

Activity concentrations of (210)Po and (210)Pb in the species Mytilus galloprovincialis from Croatian Adriatic coast were determined. The samples were collected in thirteen sampling places which are also a part of Croatian Mediterranean mussel watch project. The results of (210)Po and (210)Pb activity concentrations were found to vary between (22.1±2.5)-(207±21) Bq kg(-1) fresh weight and (2.8±1.4)-(9.3±0.7) Bq kg(-1) fresh weight, respectively. (210)Po/(210)Pb ratio ranged between 6.2 and 30.7. The highest measured activities were found in the enclosed basins of the Neretva channel, where the majority of Croatian mussel cultivation is taking place. The estimated consequent average total annual effective ingestion dose due to (210)Po and (210)Pb from mussel consumption in Croatian coastal region is 202±99 µSv with 96% contribution of (210)Po to the total effective dose.