Richard Bernhard Richardson

Canadian Nuclear Laboratories | AECL · Radiobiology and Health

It has been more than 60 years since the discovery of the oxygen effect that empirically demonstrates the direct association between cell radiosensitivity and oxygen tension, important parameters in radiotherapy. Yet the mechanisms underlying this principal tenet of radiobiology are poorly understood. Better understanding of the oxygen effect may e...

Purpose: The role of bone marrow-derived mesenchymal stem/stromal cells (MSCs) in creating a permissive microenvironment that supports the emergence and progression of acute myeloid leukemia (AML) is not well established. We investigated the extent to which adipogenic differentiation in normal MSCs alters hematopoietic supportive capacity and we u...

Domination of cell proliferation over cell death is a driving force for carcinogenesis, whereas reduced cell proliferation and increased cell death are characteristic of ageing. We employed published data to estimate representative mean values of cell turnover times for 31 different organs and tissues in adult humans and animals (when data in human...

TP53's role as guardian of the genome diminishes with age, as the probability of mutation increases. Previous studies have shown an association between p53 gene mutations and cancer. However, the role of somatic TP53 mutations in the steep rise in cancer rates with aging has not been investigated at a population level. This relationship was quantif...

This paper reviews the contemporary evidence that radiation can accelerate aging, degenerative health effects and mortality. Around the 1960s, the idea that ionizing radiation caused premature aging was dismissed as the radiation-induced health effects appeared to be virtually confined to neoplasms. More recently, radiation has become associated wi...

Background Alpha (α)-radiation is a ubiquitous environmental agent with epigenotoxic effects. Human exposure to α-radiation at potentially harmful levels can occur repetitively over the long term via inhalation of naturally occurring radon gas that accumulates in enclosed spaces, or as a result of a single exposure from a nuclear accident. Alterati...

Previous publications describe the estimation of the dose from ionizing radiation to the whole lens or parts of it but have not considered other eye tissues that are implicated in cataract development; this is especially critical for low-dose, low-ionizing-density exposures. A recent review of the biological mechanisms of radiation-induced cataract...

Although circadian biorhythms of mitochondria and cells are highly conserved and crucial for the well-being of complex animals, there is a paucity of studies on the reciprocal interactions between oxidative stress, redox modifications, metabolism, thermoregulation, and other major oscillatory physiological processes. To address this limitation, we...

Background: Exposure to different forms of ionizing radiation occurs in diverse occupational, medical, and environmental settings. Improving the accuracy of the estimated health risks associated with exposure is therefore, essential for protecting the public, particularly as it relates to chronic low dose exposures. A key aspect to understanding h...

There is a dearth of evidence-based reports linking the generation of free radicals and associated redox modifications with other major physiological changes of the sleep-wake cycle. To address this shortcoming, we examine and hypothesize that circadian/ultradian interaction of the redoxome, bioenergetics, and thermal signaling strongly regulate th...

This article explores the role that oxygen levels in US spacecraft from 1961 to 1998 have on the development of cataracts induced by space radiation in astronauts and whether oxygen levels are well accounted for in experimental studies examining cataractogenesis. The first epidemiological report in 2001 linked an increased risk of the primary types...

Theoretical evaluations indicate the radiation weighting factor for thermal neutrons differs from the current International Commission on Radiological Protection (ICRP) recommended value of 2.5, which has radiation protection implications for high-energy radiotherapy, inside spacecraft, on the lunar or Martian surface, and in nuclear reactor workpl...

The age-specific trend of cancer incidence rates, but not its magnitude, is well described employing the multistage theory of carcinogenesis by Armitage and Doll in combination with the senescence model of Pompei and Wilson. We derived empirical parameters of the multistage-senescence model from U.S. Surveillance, Epidemiology, and End Results (SEE...

Cells exposed to fast neutrons often exhibit a non-Poisson distribution of chromosome aberrations due to the high ionization density of the secondary reaction products. However, it is unknown whether lymphocytes exposed to californium-252 (252Cf) spectrum neutrons, of mean energy 2.1 MeV, demonstrate this same dispersion effect at low doses. Furthe...

Mitochondria are highly dynamic organelles. Alterations in mitochondrial dynamics are causal or are linked to numerous neurodegenerative, neuromuscular, and metabolic diseases. It is generally thought that cells with altered mitochondrial structure are prone to mitochondrial dysfunction, increased reactive oxygen species generation and widespread o...

Purpose: Since the exact development of posterior subcapsular cataracts (PSCs) is poorly understood, we review various risk factors and propose a two-stage etiology for PSCs. Methods: The biological mechanisms associated with age-related cataracts (primarily nuclear cataracts, cortical cataracts and PSCs) were reviewed in relation to selected ri...

Mitochondria are highly dynamic organelles that respond rapidly to a number of stressors to regulate energy transduction, cell death signaling, and reactive oxygen species generation. We hypothesized that mitochondrial remodeling, comprising both structural and functional alterations, following ionizing radiation (IR) may underlie some of the tenet...

Purpose: Health risks associated with the exposure of humans to low-dose ionizing radiation are currently estimated using the Linear-No-Threshold model. Over the last few decades, however, this model has been widely criticized for inconsistency with a large body of experimental evidence. Substantial efforts have been made to delineate biological me...

Elevated metabolism is a key hallmark of multiple cancers, serving to fulfill high anabolic demands. Ovarian cancer (OVCA) is the fifth leading cause of cancer deaths in women with a high mortality rate (45%). Chemoresistance is a major hurdle for OVCA treatment. Although substantial evidence suggests that metabolic reprogramming contributes to ant...

Thermal neutrons are found in reactor, radiotherapy, aircraft, and space environments. The purpose of this study was to characterize the dosimetry and microdosimetry of thermal neutron exposures, using three simulation codes, as a precursor to quantitative radiobiological studies using blood samples. An irradiation line was designed employing a pyr...

Trend analysis of hourly wind direction angle recorded at nine meteorological stations across southern Canada (in the 43°-53°N belt) identified wind direction rotation periods in the range of 7-9 days. Rotation persists during the "summertime" season from May to mid-October during 1953-2001. Rotation with a 7.5-day period was also established in th...

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at...

Background The therapeutic potential of mesenchymal stromal cells (MSCs) may be largely mediated by paracrine factors contained in microvesicles (MV) released from intracellular endosomes. A systematic review of controlled interventional animal studies was performed to identify models of organ injury where clinical translation of MSC-derived micro...

A radiological concern for workers at heavy water reactor nuclear facilities is the hazard presented by tritium (H) and C. Radioactive methane is one of many potential H and C containing chemicals to which Nuclear Energy Workers (NEWs) may be exposed. Current dosimetric models for H- and C-methane, recommended by the International Commission on Rad...

Knudson's carcinogenic model, which simulates incidence rates for retinoblastoma, provides compelling evidence for a two-stage mutational process. However, for more complex cancers, existing multistage models are less convincing. To fill this gap, I hypothesize that neoplasms preferentially arise when stem cell exhaustion creates a short supply of...

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marro...

The good neutron economy and online refueling capability of the CANDU® heavy water moderated reactor (HWR) enable it to use many different fuels such as low enriched uranium (LEU), plutonium, or thorium, in addition to its traditional natural uranium (NU) fuel. The toxicity and radiological protection methods for these proposed fuels, unlike those...

This paper describes a methodology for assessing the pre-mission exposure of space crew aboard the International Space Station (ISS) in terms of an effective dose equivalent. In this approach, the PHITS Monte Carlo code was used to assess the particle transport of galactic cosmic radiation (GCR) and trapped radiation for solar maximum and minimum c...

Hourly surface observations from the Canadian Weather Energy and Engineering Dataset were analyzed with respect to long-term wind direction drift or rotation. Most of the Canadian landmass, including the High Arctic, exhibits a spatially consistent and remarkably steady anticyclonic rotation of wind direction. The period of anticyclonic rotation re...

This paper speculates on the role of infection in modifying a young child's risk of promoting precursor B-cell acute lymphoblastic leukemia (ALL). It is suggested that the heat shock instigated by infections, particularly in infancy, stimulates Th1 pro-inflammatory cytokines and an apoptosis-inhibitory environment. This infective stress also increa...

Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation. Conclusions: The hypoxic conditions of the 10 μm thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside p...

When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at...

Following a radiation emergency, the affected public and the first responders may need to be quickly assessed for internal contamination by the radionuclides involved. Urine bioassay is one of the most commonly used methods for assessing radionuclide intake and radiation dose. This paper attempts to derive the sensitivity requirements (from inhalat...

A physiological skeletal model (PSM) is described that represents the skeletal uptake, retention, and clearance of both bone-surface-seeking and bone-volume-seeking radionuclides and stable elements. A key objective of the PSM is to model the higher skeletal growth and bone turnover in infants and children (compared to adults) in order to account f...

The Workshop on Emergency Preparedness for Vulnerable Population Groups was held on 2 and 3 March 2009 in Ottawa, ON, Canada. The purpose of the workshop was to enhance communications within the emergency community response network and to identify the needs and gaps of emergency preparedness against chemical, biological, radiological, nuclear and e...

The factors that influence the dose and risk to vulnerable population groups from exposure and internal uptake of chemicals are examined and, in particular, the radionuclides released in chemical, biological, radiological, nuclear and explosive events. The paper seeks to identify the areas that would benefit from further research. The intake and bo...

A Monte Carlo simulation of repeated cubic units representing trabecular bone cavities in adult bone was employed to determine absorbed dose fractions evaluated for (3)H, (14)C and a set of alpha-emitters incorporated within a bone remodeling compartment (BRC). The BRC consists of a well-oxygenated vascular microenvironment located within a canopy...

The aim is to study the implications of the decrease in oxygen concentration in the coronary artery walls with age and atherosclerosis, particularly with regard to an associated reduction in the radiosensitivity to high-and low-linear-energy-transfer (LET) irradiation. In accompanying papers, the age-dependent morphology and composition for the wal...

There is mounting evidence that a significant fraction of radiation-induced mortality and years-life lost are non-cancerous in nature. This study quantifies the radon dose to the coronary artery walls, especially the intimal layer, vulnerable to the development of atherosclerosis, and associated cardiovascular disease (CVD). Two accompanying papers...

The aim is to assess the change with age and disease of the oxygen concentration within the coronary artery walls. In an accompanying paper, Part A, the age-dependent morphology and composition for the wall layers of normal and diseased coronary arteries were developed from published data. In this paper, Part B, the oxygen concentration in the coro...

Theoretical and experimental methods were developed to assess the size distribution of alpha-emitting particles captured on air-sampler filters. The particle size of oxides of low enriched, depleted and natural uranium and also aged plutonium in mixed oxide reactor fuels of known composition was determined using poly-allyl-diglycol carbonate (PADC)...

A Monte Carlo simulation of multiple trabecular bone cavities in adult bone was developed and the absorbed radiation dose factors evaluated for 3H and 14C. The model was developed to assess the dose from radionuclide uptake in quiescent bone, but also the effects of temporal changes in bone turnover by incorporating bone-modelling units (BMU). Abso...

Radon is a naturally occurring radioactive gas. When it is inhaled, a significant proportion of the radon and its progeny deposited in the lung are absorbed into the blood. The absorbed radon delivers radiation doses to all tissues or organs. The thin inner layer of the coronary arteries is probably the primary target tissue of radiation-induced at...

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In this paper the physiological criteria for a novel form of model are described whose biokinetics are governed by the overall metabolic reactions of the principal nutrients: carbohydrates, fats, and proteins. The biokinetics of a particular element are based primarily on the oxidation of glucose, fatty acids, and amino acids and the formation of w...

In this paper the dosimetry for a novel form of physiological model, whose biokinetics are governed by the overall metabolic reactions of the principal nutrients carbohydrates, fats and proteins, is evaluated by compartmental analysis. Two models of differing complexity, called the HCNO-S and HCNO-C models, were developed from parameters evaluated...

Monte Carlo simulations were carried out to calculate the age-dependent dose from the beta decay of 14C to marrow and bone on the basis of a steady-state specific-activity model. A model of the trabecular cavity containing spherical fat cells in a square lattice surrounded by haemopoietic tissue was employed. The age-dependent 14C dose to haemopoie...

Methods have been developed to assess the size distribution of alpha emitting particles of reactor fuel of known composition captured on air sampler filters. The sizes of uranium oxide and plutonium oxide particles were determined using a system based on CR-39 solid-state nuclear track detectors. The CR-39 plastic was exposed to the deposited parti...

Biokinetic models for tritium and 14C compounds, as described by various ICRP publications, have been incorporated into the Genmod-PC internal dosimetry code. This work reviews the models for tritium and 14C labeled compounds that the ICRP has formulated over several decades. The ICRP dosimetry prescribed for hydrogen and carbon radionuclides is fu...

The ICRP's biokinetic models for five tritium-labeled and five 14C-labeled compounds (not including radiopharmaceutical compounds and excepting carbon monoxide) incorporate a compartment representing the body carbon pool. Using the ICRP models, as coded into the Genmod-PC internal dosimetry code, higher dose coefficients are calculated for females...

Tritiated particulate materials are of potential hazard in fission, fusion, and other tritium handling facilities. The absorbed fractions (fraction of energy emitted that is absorbed by the target region) are calculated for tritiated particles deposited in the alveolar-interstitial (AI) region of the respiratory tract. The energy absorbed by radiol...

A Monte Carlo simulation of tritium decays in a cell composed of two parts, a nucleus and surrounding cytoplasm, was developed to evaluate the beta-radiation dose to the nucleus. A dose modifying factor (DMF), which is a ratio of the average nuclear dose to the whole-tissue dose, after skin-contact exposure of rats to tritiated pump oil or tritiate...

Genmod was initially developed by Johnson and Dunford to perform internal dose assessments and evaluate bioassay data using the methods described by the ICRP in Publications 26 and 30. The mainframe code, Genmod-MF was modified to implement the ICRP's new lung model, new weighting factors and new values for specific effective energy (SEE) available...

Urine samples from eight male radiation workers who had an unplanned acute tritiated water intake were measured for tritium-in-urine up to 300 d post-exposure. During the first month or so post-exposure, these individuals increased their fluid intakes to accelerate the turnover rate of tritium in the body for dose mitigation. Their daily fluid inta...

Tritiated water (HTO) represents the most important occupational and environmental exposures to tritium, as far as radiation protection is concerned. This paper studies the dynamics of HTO and organically bound tritium (OBT) in urine, feces and blood from male workers at 100-300 following an acute intake of HTO. It is indicated that the activity co...

Because of the paucity of actual measurements, a theoretical model has been developed that predicts the in utero activity levels of 210Po ingrowing from 210Pb. Experimental data have shown that the placental transfer of lead takes place, but precludes the transfer of significant amounts of polonium. Bone volume seekers with long half-lives that can...

A survey of the literature regarding the biomedical properties of inhaled short-lived decay products of radon showed that the importance of the physical, biochemical and biokinetic properties of bismuth radionuclides have been greatly overlooked, especially in the prenatal and preconception stages of human development. As no data are available on t...

The age-dependent radiation dose to the haematopoietic tissue of bone marrow has been calculated for exposure to radon, thoron and their daughter products, for the foetus, children and adults. The component of dose due to pure radon is dependent on the fat content of the marrow, since the solubility of radon in fat is about sixteen times that in ti...

The age-dependent radiation dose to the haematopoietic tissue of bone marrow has been calculated for exposure to radon, thoron and their daughter products, for the foetus, children and adults. The component of dose due to pure radon is dependent on the fat content of the marrow, since the solubility of radon in fat is about sixteen times that in ti...

The age-dependent radiation dose to the haematopoietic tissue of bone marrow has been calculated for exposure to radon, thoron and their daughter products. The component of dose due to pure radon is dependent on the fat content of the marrow, since the solubility of radon in fat is about 16 times that in tissue. The mean dose equivalent μSv to the...

Fifteen patients with neoplastic meningitis received a single intrathecal injection of between 11 and 60 mCi of a 131I radiolabelled monoclonal antibody (MoAb), chosen for its immunoreactivity to tumour. Major toxicity was manifest as nausea, vomiting and headache (7/15 patients), reversible bone marrow suppression (3/8 patients) and seizures (2/15...

The present is a time of great change in the assessment of radiation risk and its influence on dose limits. The main sources of risk estimates arise from irradiation for medical reasons and from the use of atomic weapons. The effects of radiation on humans and animals are reviewed by such august bodies as the International Commission on Radiologica...

The international incidence of myeloid leukaemia, cancer of the kidney, melanoma, and certain childhood cancers all show significant correlation with radon exposure in the home. For myeloid leukaemia, analysis suggests that in the UK 6-12% of incidence may be attributed to radon. In Cornwall, where radon levels are higher, the range is 23-43%. For...

Radioiodinated monoclonal antibodies (MCA) were administered by the lumbar route into the cerebrospinal fluid (CSF) of four patients with malignant leptomeningeal disease. Evidence suggesting uptake of 131I-MCA by tumour sites was seen in scintigrams. Dosimetry calculations were carried out, assuming that a proportion of the administered radionucli...

A pilot study was performed to investigate the toxicity and therapeutic effect of radiolabeled antibody administered intrathecally in patients with leptomeningeal tumors. Five patients who failed conventional therapy received between 11 mCi and 40 mCi of radiolabeled antibody. The choice of antibody varied depending on the immunophenotype of the tu...

A monoclonal antibody (UJ181.4) was labelled with 131I and given intrathecally to a patient who was critically ill with neoplastic meningitis due to a disseminated pineoblastoma. The target antigen had first been demonstrated on tumour cells by immunocytological testing of cerebrospinal fluid (CSF). As a preparation for therapy, a test dose of 131I...

In a single-centre prospective trial 200 consecutive patients undergoing thoracic surgery were randomised to receive one of two prophylactic regimes against deep vein thrombosis (DVT). These were 5000 units of subcutaneous heparin twice a day, alone or combined with the wearing of graded compression stockings. The diagnosis of DVT was made clinical...

Over recent years we have been studying the possibility of targeting radiolabelled monoclonal antibodies to human brain tumours in vivo. This work began with the development of panels of monoclonal antibodies for use in the diagnosis of brain tumour biopsies and cerebrospinal fluid infiltrates (1). Certain of these antibodies were then chosen for u...

A portable peak flow meter based on a turbine transducer that can display results in code has been developed. Its performance compares well with the Wright peak flow meter. Records of subjective self assessment of asthma on a visual analogue scale and of peak flow (PEF) were compared in 12 subjects with asthma. PEF measurements were made with a cod...

Skin blood flow as reflected by the clearance rate of intradermal injections of Technetium-99m (99mTc) was studied in the skin of human volunteers and in a variety of clinical situations. In volunteers comparisons between the effect on clearance following intradermal injections of either lignocaine or lignocaine/adrenaline showed that the latter re...

The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to...

Monoclonal antibody UJ13A, radiolabelled with 131I, was intravenously administered to patients with primary brain tumours. The antigen recognised by UJ13A is present on most neuroectodermally derived tissue. The ratio of uptake in tumour to normal brain, assessed by scintigraphy, improved with time. Maximal tumour uptake occurred between 4 and 48 h...