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Biomedical subjects

B R Scott

Publications and source records attributed to B R Scott.

At least 19 recordsLinked to original sources
PubMed2006

Influence of alpha and gamma radiations and non-radiation risk factors on the incidence of malignant liver tumors among Mayak PA workers.

This Mayak worker-based study focuses on evaluating possible associations between malignant liver cancers and chronic alpha irradiation, chronic gamma irradiation, and non-radiation risk factors (alcohol consumption, smoking, viral hepatitis, chemical exposure, and chronic digestive diseases). This is the first multivariate study related to liver cancer among Mayak workers. The study was performed using the nested, case-control approach and includes 44 cases of malignant liver tumors diagnosed from 1972 to 1999, and 111 matched controls. Adjusted odds ratio (OR(ad)) was evaluated relative to a group of workers with alpha radiation doses to liver (D(alpha)) < 2.0 Gy. Dose estimates of D(alpha) > 2.0 Gy (corresponding (239)Pu body burden estimates >20.4 kBq) were significantly associated (p < 0.003) with the occurrence of hemangiosarcomas (HAS) but only marginal significance (0.05 < p < 0.1) was found for hepatocellular cancers (HCC). The ORad for HAS was 41.7 [95% confidence interval (CI): 4.6, 333] for a group with D(alpha) in the range >2.0-5.0 Gy and was 62.5 (7.4, 500) for a group with D(alpha) > 5.0-16.9 Gy. The attributable risk (AR) was calculated as 82%. For HCC, O(Rad) was estimated as 8.4 (0.8, 85.3; p < 0.07) for a group with D(alpha) in the range >2.0-9.3 Gy. For the indicated group, the AR was 14%. An association with high external gamma-ray doses (D(gamma)) to the total body was revealed for both HCC and for combined liver cancers when dose was treated as a continuous variable. However, we find no evidence that chronic low doses of gamma rays are associated with liver cancer occurrence. Cholangiocarcinoma (CHC) was not associated with either alpha- or gamma-ray exposure. As expected, an association between alcohol abuse and HCC was inferred [O(Rad) = 3.3 (1.2, 9); AR = 41%] but not for CHC or HAS.

Alpha Particles↗
PubMed2004

Chromosomal aberrations in lymphocytes of peripheral blood among Mayak facility workers who inhaled insoluble forms of 239PU.

A cytogenetic study was performed on 79 plutonium (Pu) workers chronically exposed to alpha radiation from inhaled, low-transportable (insoluble) compounds of airborne 239Pu and to external gamma rays. Body burden estimates for 239Pu ranged from 0 to 15.5 kBq. Chromosomal aberrations (CAs) (stable and unstable) among peripheral blood lymphocytes and cumulative alpha radiation doses were evaluated approximately 25 y after first contact with 239Pu. For the cytogenetic analyses, a standard two-day peripheral blood lymphocyte culture technique was applied. While alpha radiation doses continually increase up to the time of cytogenetic measurements, significant gamma ray exposures essentially ceased long before the time of measurement, so that alpha and gamma doses were not correlated. For the exposed workers, the mean 239Pu body burden (estimate), evaluated at the time of the cytogenetic measurement, was 1.23 +/- 0.26 kBq and the corresponding mean absorbed external gamma ray dose (estimate) to the total body was 0.076 +/- 0.009 Gy. Single and multivariate regression analyses were performed on the CA data. Stable, unstable and total aberrations increased as the 239Pu body burden increased over the range 0-4.5 kBq. However, above this range little additional increase was observed. CAs were weakly correlated with time since the first intake of 239Pu. No relationship between chromatid aberrations and 239Pu incorporation was found. Unstable (but not stable) aberrations were correlated with gamma radiation dose. No significant relationship of CA and smoking was found.

Adult↗
PubMed2004

A biological-based model that links genomic instability, bystander effects, and adaptive response.

This paper links genomic instability, bystander effects, and adaptive response in mammalian cell communities via a novel biological-based, dose-response model called NEOTRANS3. The model is an extension of the NEOTRANS2 model that addressed stochastic effects (genomic instability, mutations, and neoplastic transformation) associated with brief exposure to low radiation doses. With both models, ionizing radiation produces DNA damage in cells that can be associated with varying degrees of genomic instability. Cells with persistent problematic instability (PPI) are mutants that arise via misrepair of DNA damage. Progeny of PPI cells also have PPI and can undergo spontaneous neoplastic transformation. Unlike NEOTRANS2, with NEOTRANS3 newly induced mutant PPI cells and their neoplastically transformed progeny can be suppressed via our previously introduced protective apoptosis-mediated (PAM) process, which can be activated by low linear energy transfer (LET) radiation. However, with NEOTRANS3 (which like NEOTRANS2 involves cross-talk between nongenomically compromised [e.g., nontransformed, nonmutants] and genomically compromised [e.g., mutants, transformants, etc.] cells), it is assumed that PAM is only activated over a relatively narrow, dose-rate-dependent interval (D(PAM),D(off)); where D(PAM) is a small stochastic activation threshold, and D(off) is the stochastic dose above which PAM does not occur. PAM cooperates with activated normal DNA repair and with activated normal apoptosis in guarding against genomic instability. Normal repair involves both error-free repair and misrepair components. Normal apoptosis and the error-free component of normal repair protect mammals by preventing the occurrence of mutant cells. PAM selectively removes mutant cells arising via the misrepair component of normal repair, selectively removes existing neoplastically transformed cells, and probably selectively removes other genomically compromised cells when it is activated. PAM likely involves multiple pathways to apoptosis, with the selected pathway depending on the type of cell to be removed, its cellular environment, and on the nature of the genomic damage.

Animals↗
PubMed2002

Respiratory tract deposition efficiencies: evaluation of effects from smoke released in the Cerro Grande forest fire.

Forest-fire smoke inhaled by humans can cause various health effects. This smoke contains toxic chemicals and naturally occurring radionuclides. In northern New Mexico, a large wildfire occurred in May 2000. Known as the Cerro Grande Fire, it devastated the town of Los Alamos and damaged Los Alamos National Laboratory (LANL). Residents were concerned about the possible dissemination of radionuclides from LANL via smoke from the fire. To evaluate potential health effects of inhaling radionuclides contained in the smoke from the Cerro Grande Fire, it was first necessary to evaluate how much smoke would deposit in the human respiratory tract. The purpose of this study was to evaluate respiratory-tract deposition efficiencies of airborne forest-fire smoke for persons of different ages exposed while inside their homes. Potential non-radiological health effects of a forest fire are reviewed. The deposition efficiencies presented can be used to evaluate in-home smoke deposition in the respiratory tract and expected radionuclide intake related to forest fires. The impact of smoke exposure on firemen fighting a forest fire is quantitatively discussed and compared. They primarily inhaled forest-fire smoke while outdoors where the smoke concentration was much higher than inside. Radionuclides released at the LANL site via the Cerro Grande Fire were restricted to naturally occurring radionuclides from burning trees and vegetation. Radiation doses from inhaled airborne radionuclides to individuals inside and outside the Los Alamos area were likely very small.

Adult↗
PubMed2002

Interaction of radiation and smoking in lung cancer induction among workers at the Mayak nuclear enterprise.

For radiation-related cancer risk evaluation, it is important to assess not only influences of individual risk factors but also their interactive effects (e.g., additive, multiplicative, etc.). Multivariate analysis methods adapted for interactive effects allow such assessments. We have used a multivariate analysis approach to investigate the pair-wise interactions of the previously identified three main etiological factors for lung cancer induction in Russian workers of the Mayak Production Association (PA) nuclear enterprise. These three factors are as follows: (1) body burden of inhaled plutonium-239 (239Pu), an influence on absorbed alpha-radiation dose; (2) cumulative, absorbed external gamma-radiation dose to the lung; and (3) level of cigarette smoking as indicated by a smoking index (SI). The SI represents the cigarettes smoked per day times years smoking. The Mayak PA workers were exposed by inhalation to both soluble and insoluble forms of 239Pu. Based on a cohort of 4,390 persons (77% male), we conducted a nested, case-control study of lung cancer induction using 486 matched cases and controls. Each case was matched to two controls. Matching was based on five factors: sex, year of birth, year work began, profession, and workplace. Three levels of smoking were considered: low (SI = 1 to 499), used as a reference level; middle (SI = 500 to 900); and high (SI = 901 to 2,000). For lung cancer induction, a supra-multiplicative effect was demonstrated for high external gamma-ray doses (> 2.0 Gy) plus high 239Pu intakes (body burden >2.3 kBq). This observation is consistent with the hypothesis of curvilinear dose-response relationships for lung cancer induction by high- and low-LET radiations. The interaction between radiation (external gamma rays or 239Pu body burden) and cigarette smoke was found to depend on the smoking level. For the middle level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with additive effects. However, for the high level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with the occurrence of multiplicative effects. These results indicate that low-dose risk estimates for radiation-induced lung cancer derived without adjusting for the influence of cigarette smoking could be greatly overestimated. Further, such systematic error may considerably distort the shape of the risk vs. dose curve and could possibly obscure the presence of a dose threshold for radiation-induced lung cancer.

Aged↗
PubMed2001

The N-terminal globular domain and the first class A amphipathic helix of apolipoprotein A-I are important for lecithin:cholesterol acyltransferase activation and the maturation of high density lipoprotein in vivo.

To investigate the role of the N terminus of apolipoprotein A-I (apoA-I) in the maturation of high density lipoproteins (HDL), two N-terminal mutants with deletions of residues 1-43 and 1-65 (referred to as Delta 1-43 and Delta 1-65 apoA-I) were studied. In vitro, these deletions had little effect on cellular cholesterol efflux from macrophages but LCAT activation was reduced by 50 and 70% for the Delta 1-43 and Delta 1-65 apoA-I mutants, respectively, relative to wild-type (Wt) apoA-I. To further define the role of the N terminus of apoA-I in HDL maturation, we constructed recombinant adenoviruses containing Wt apoA-I and two similar mutants with deletions of residues 7-43 and 7-65 (referred to as Delta 7-43 and Delta 7-65 apoA-I, respectively). Residues 1-6 were not removed in these mutants to allow proper cleavage of the pro-sequence in vivo. Following injection of these adenoviruses into apoA-I-deficient mice, plasma concentrations of both Delta 7-43 and Delta 7-65 apoA-I were reduced 4-fold relative to Wt apoA-I. The N-terminal deletion mutants, in particular Delta 7-65 apoA-I, were associated with greater proportions of pre beta-HDL and accumulated fewer HDL cholesteryl esters relative to Wt apoA-I. Wt and Delta 7-43 apoA-I formed predominantly alpha-migrating and spherical HDL, whereas Delta 7-65 apoA-I formed only pre beta-HDL of discoidal morphology. This demonstrates that deletion of the first class A amphipathic alpha-helix has a profound additive effect in vivo over the deletion of the globular domain alone (amino acids 1-43) indicating its important role in the production of mature alpha-migrating HDL. In summary, the combined in vitro and in vivo studies demonstrate a role for the N terminus of apoA-I in lecithin:cholesterol acyltransferase activation and the requirement of the first class A amphipathic alpha-helix for the maturation of HDL in vivo.

Adenoviridae↗
PubMed2001

Proteolytic degradation and impaired secretion of an apolipoprotein A-I mutant associated with dominantly inherited hypoalphalipoproteinemia.

We have devised a combined in vivo, ex vivo, and in vitro approach to elucidate the mechanism(s) responsible for the hypoalphalipoproteinemia in heterozygous carriers of a naturally occurring apolipoprotein A-I (apoA-I) variant (Leu(159) to Arg) known as apoA-I Finland (apoA-I(FIN)). Adenovirus-mediated expression of apoA-I(FIN) decreased apoA-I and high density lipoprotein cholesterol concentrations in both wild-type C57BL/6J mice and in apoA-I-deficient mice expressing native human apoA-I (hapoA-I). Interestingly, apoA-I(FIN) was degraded in the plasma, and the extent of proteolysis correlated with the most significant reductions in murine apoA-I concentrations. ApoA-I(FIN) had impaired activation of lecithin:cholesterol acyltransferase in vitro compared with hapoA-I, but in a mixed lipoprotein preparation consisting of both hapoA-I and apoA-I(FIN) there was only a moderate reduction in the activation of this enzyme. Importantly, secretion of apoA-I was also decreased from primary apoA-I-deficient hepatocytes when hapoA-I was co-expressed with apoA-I(FIN) following infection with recombinant adenoviruses, a condition that mimics secretion in heterozygotes. Thus, this is the first demonstration of an apoA-I point mutation that decreases LCAT activation, impairs hepatocyte secretion of apoA-I, and makes apoA-I susceptible to proteolysis leading to dominantly inherited hypoalphalipoproteinemia.

Amino Acid Substitution↗
PubMed2001

Application of Bayesian inference to characterize risks associated with low doses of low-LET radiation.

Improved risk characterization for stochastic biological effects of low doses of low-LET radiation is important for protecting nuclear workers and the public from harm from radiation exposure. Here we present a Bayesian approach to characterize risks of stochastic effects from low doses of low-LET radiation. The stochastic effect considered is neoplastic transformation of cells because it relates closely to cancer induction. We have used a published model of neoplastic transformation called NEOTRANS1. It is based on two different classes of cellular sensitivity for asynchronous, exponentially growing populations (in vitro). One sensitivity class is the hypersensitive cell; the other is the resistant cell. NEOTRANS1 includes the effects of genomic damage accumulation, DNA repair during cell cycle arrest, and DNA misrepair (non-lethal repair errors). The model-associated differential equations are solved for conditions of in vitro irradiation at a fixed rate. Previously published solutions apply only to high dose rates and were incorrectly assumed to apply to only high-LET radiation. Solutions provided here apply to any fixed dose rate and to both high- and low-LET radiations. Markov chain Monte Carlo methods are used to carry out the Bayesian inference of the low-dose risk for neoplastic transformation of aneuploid C3H 10T1/2 cells for X-ray doses from 0 to 1000 mGy. We have assumed that for this low-dose range only the hypersensitive fraction of the cells are affected. Our results indicate that the initial slope of the risk vs dose relationship for neoplastic transformation is as follows: (1) directly proportional to the fraction, f1, of hypersensitive cells; (2) directly proportional to the radiosensitivity of the genomic target; and (3) inversely proportional to the rate at which hypersensitive cells with radiation-induced damage are committed to undergo correct repair of genomic damage. Further, our results indicate that very fast molecular events are associated with the commitment of cells to the correct repair pathway. Results also indicate a relatively large probability for misrepair that leads to genomic instability. Our results are consistent with the view that for very low doses, dose rate is not an important variable for characterizing low-LET radiation risks so long as age-related changes in sensitivity do not occur during irradiation.

Animals↗
PubMed2001

Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system.

Ethanol consumption and cigarette smoking are common in societies worldwide and have been identified as injurious to human health. This study was undertaken to examine the interactive effects of chronic ethanol and nicotine consumption on the antioxidant defense system in different tissues of rat. Male Fisher-344 rats were divided into four groups of five animals each and treated for 6.5 weeks as follows: (1) Control rats were administered normal saline orally; (2) ethanol (20% [wt./vol.]) was given orally at a dose of 2 g/kg; (3) nicotine was administered subcutaneously at a dose of 0.1 mg/kg; and (4) a combination of ethanol plus nicotine was administered by the route and at the dose described above. The animals were killed 20 h after the last treatment, and liver, lung, kidney, and testes were isolated and analyzed. Chronic ingestion of ethanol resulted in a significant depletion of glutathione (GSH) content in liver, lung, and testes, whereas chronic administration of nicotine significantly depleted GSH content in liver and testes. The combination of ethanol plus nicotine resulted in a significant depletion of GSH content in liver, lung, and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased superoxide dismutase (SOD) activity in liver and decreased SOD activity in kidney. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly decreased catalase (CAT) activity in liver and increased CAT activity in kidney and testes. Chronic ingestion of ethanol resulted in a significant decrease in glutathione peroxidase (GSH-Px) activity in liver and kidney, whereas a combination of ethanol plus nicotine increased GSH-Px activity in liver and decreased GSH-Px activity in kidney and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased lipid peroxidation, respectively, in liver. It is suggested that prolonged exposure to ethanol and nicotine produce similar, and in some cases additive, oxidative tissue injuries in rat.

Animals↗
PubMed2001

A model for absorption of low-volatile toxicants by the airway mucosa.

Inhaled chemical toxicants can damage the lungs during two phases: (1) the first-pass phase, in which toxicants are initially absorbed through the air/blood barrier, or (2) the circulation-transport phase, in which toxicants are transported back through the lungs with the circulating blood. While respiratory-tract dosimetry for inhaled toxicants is relatively easy to evaluate for the circulation-transport phase, it is more problematic for the first-pass phase and can involve higher local concentrations of toxicants. This article describes a respiratory-tract dosimetry model that simulates both the rate of absorption and the local concentration of low-volatile organic toxicants in the airway mucosa. The model simulates the non-steady-state diffusion of organic solutes from the air interface through the epithelium and into the capillary bed below. Cellular tissues are described as a heterogeneous, two-phase medium, with a minor lipid phase dispersed in a major aqueous phase. Results show that the lipid-phase/aqueous-phase partition coefficient, PC(L/A), is a critical factor in determining the rate of absorption of solutes in the airway mucosa. For a PC(L/A) in the range 1 to 100, absorption is limited by blood flow and occurs with typical half-times from about 1 to 10 min. As PC(L/A) increases above 100, absorption is gradually limited by the rate of diffusion through the air/blood barrier, and absorption half-times increase to hours. Over the same range, the concentration gradient in the mucosa changes from almost uniform to more nonuniform, and the site-of-entry epithelium becomes more selectively exposed. As a result, with increasing PC(L/A), protoxicants of lower reactivities can still be activated in significant quantities in the airway epithelium and thus act as site-of-entry toxicants. The presented results are important for understanding exposure/target-dose relationships of chemical carcinogens and for conducting reliable risk assessments.

Absorption↗
PubMed2000

Distinct central amphipathic alpha-helices in apolipoprotein A-I contribute to the in vivo maturation of high density lipoprotein by either activating lecithin-cholesterol acyltransferase or binding lipids.

Recombinant adenoviruses with cDNAs for human apolipoprotein A-I (wild type (wt) apoA-I) and three mutants, referred to as Delta4-5A-I, Delta5-6A-I, and Delta6-7A-I, that have deletions removing regions coding for amino acids 100-143, 122-165, and 144-186, respectively, were created to study structure/function relationships of apoA-I in vivo. All mutants were expressed at lower concentrations than wt apoA-I in plasma of fasting apoA-I-deficient mice. The Delta5-6A-I mutant was found primarily in the lipid-poor high density lipoprotein (HDL) pool and at lower concentrations than Delta4-5A-I and Delta6-7A-I that formed more buoyant HDL(2/3) particles. At an elevated adenovirus dose and earlier blood sampling from fed mice, both Delta5-6A-I and Delta6-7A-I increased HDL-free cholesterol and phospholipid but not cholesteryl ester. In contrast, wt apoA-I and Delta4-5A-I produced significant increases in HDL cholesteryl ester. Further analysis showed that Delta6-7A-I and native apoA-I could bind similar amounts of phospholipid and cholesterol that were reduced slightly for Delta5-6A-I and greatly for Delta4-5A-I. We conclude from these findings that amino acids (aa) 100-143, specifically helix 4 (aa 100-121), contributes to the maturation of HDL through a role in lipid binding and that the downstream sequence (aa 144-186) centered around helix 6 (aa 144-165) is responsible for the activation of lecithin-cholesterol acyltransferase.

Animals↗
PubMed2000

Deterministic effects from occupational radiation exposures in a cohort of Mayak PA workers: data base description.

Project 2.3 of the Joint Coordinating Committee on Radiation Effects Research (JCCRER) is a study of deterministic health effects among a cohort of Russia nuclear workers. The preliminary study population includes a stratified random sample of 221 radiation workers who were employed in a cohort of 8,055 workers at the Mayak PA facilities for at least one year during the period from 1948 to 1958. High annual doses, approaching 1 Gy per year from external and internal radiation sources, were reported for a significant proportion of the workers in this cohort. The present data set includes 96 cases of chronic radiation sickness (CRS), 14 cases of acute radiation syndrome (ARS) and 13 cases of plutonium pneumosclerosis (PPn). The remainder of the sample consists of "uninjured workers" who had no known history of radiation illness or injury; however, the uninjured workers are not "controls" for radiation exposure. The data base is currently being expanded to 600 individuals sampled from the cohort of workers from 1948 to 1958 to allow a more complete analysis of the deterministic health effects and comparisons with existing health effect models. The final data base will be used with state-of-the-art modeling techniques to determine threshold doses and dose-response relationships for key clinical diagnostic variables.

Acute Disease↗
PubMed1998

Evaluating the risk of death via the hematopoietic syndrome mode for prolonged exposure of nuclear workers to radiation delivered at very low rates.

During a Phase-I effort, studies were planned to evaluate deterministic (nonstochastic) effects of chronic exposure of nuclear workers at the Mayak atomic complex in the former Soviet Union to relatively high levels (> 0.25 Gy) of ionizing radiation. The Mayak complex has been used, since the late 1940's, to produce plutonium for nuclear weapons. Workers at Site A of the complex were involved in plutonium breeding using nuclear reactors, and some were exposed to relatively large doses of gamma rays plus relatively small neutron doses. The Weibull normalized-dose model, which has been set up to evaluate the risk of specific deterministic effects of combined, continuous exposure of humans to alpha, beta, and gamma radiations, is here adapted for chronic exposure to gamma rays and neutrons during repeated 6-h work shifts--as occurred for some nuclear workers at Site A. Using the adapted model, key conclusions were reached that will facilitate a Phase-II study of deterministic effects among Mayak workers. These conclusions include the following: (1) neutron doses may be more important for Mayak workers than for Japanese A-bomb victims in Hiroshima and can be accounted for using an adjusted dose (which accounts for neutron relative biological effectiveness); (2) to account for dose-rate effects, normalized dose X (a dimensionless fraction of an LD50 or ED50) can be evaluated in terms of an adjusted dose; (3) nonlinear dose-response curves for the risk of death via the hematopoietic mode can be converted to linear dose-response curves (for low levels of risk) using a newly proposed dimensionless dose, D = X(V), in units of Oklad (where D is pronounced "deh"), and V is the shape parameter in the Weibull model; (4) for X < or = Xo, where Xo is the threshold normalized dose, D = 0; (5) unlike absorbed dose, the dose D can be averaged over different Mayak workers in order to calculate the average risk of death via the hematopoietic mode for the population exposed at Site A; and (6) the expected cases of death via the hematopoietic syndrome mode for Mayak workers chronically exposed during work shifts at Site A to gamma rays and neutrons can be predicted using ln(2)B M[D]; where B (pronounced "beh") is the number of workers at risk (criticality accident victims excluded); and M[D] is the average (mean) value of D (averaged over the worker population at risk, for Site A, for the time period considered). These results can be used to facilitate a Phase II study of deterministic radiation effects among Mayak workers chronically exposed to gamma rays and neutrons.

Chronic Disease↗
PubMed1996

Toxicity of inhaled plutonium dioxide in beagle dogs.

This study was conducted to determine the biological effects of inhaled 238PuO2 over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of 238PuO2 to achieve graded levels of initial lung burden (ILB). The aerosols also contained 169Yb to provide a gamma-ray-emitting label for the 238Pu inhaled by each dog. Excreta were collected periodically over each dog's life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest alpha-particle doses, ranging from 0.16-68 Gy for the lung, 0.08-8.7 Gy for the skeleton and 0.18-19 for the liver. At death all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. Bone tumors found in 93 dogs were the most common cause of death. Lung tumors found in 46 dogs were the second most common cause of death. Liver tumors, which were found in 20 dogs but were the cause of death in only two dogs, occurred later than the tumors in bone and lung. Tumors in these three organs often occurred in the same animal and were competing causes of death. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to 238PuO2.

Administration, Inhalation↗
PubMed1995

A generic model for estimating the risk of deterministic effects of partial organ irradiation by hot particles.

A generic (Weibull-type) model is presented for evaluating the risk of a specified deterministic effect of hot-particle (i.e., highly radioactive particle) exposure of the skin, eye, ear, respiratory tract, or gastrointestinal tract. The generic model is a composite of the two-parameter Weibull function used for evaluating the risk of deterministic effects of total-organ irradiation and an isoeffect equation for partial-volume (i.e., fractional-volume) irradiation. Isoeffect refers to a constant level of risk rather than a constant level of severity. The generic model provides a way to evaluate the uniform-exposure, isoeffect equivalent dose, H'T,V, to a partial volume V that incurs the same risk as is associated with a nonuniform exposure of volumes within V. When V = 1, the volume is called a reference volume. The reference volume can be associated with a specific organ or mass of tissue. The reference-volume-specific, uniform-exposure, isoeffect equivalent dose, H'T,1, can be used to limit the risk of deterministic effects of hot-particle exposure by requiring that H'T,1 remain below the equivalent dose limit for any reference volume of tissue at risk. Local doses H'T,V, can be converted to isoeffect doses H'T,1 by multiplying H'T,V by a volume weighting factor Wv, where Wv equals Vn. For deterministic effects, n < 1. For stochastic effects, n = 1. For stochastic effects, H'T,1 can be converted to an effective dose by multiplying H'T,1 by an appropriate tissue-weighting factor WT. Results presented apply to circumstances where, at most, only a few hot particles are involved. In such circumstances, it is highly unlikely that local tissue will be irradiated by more than one hot particle. Although the focus of this paper is on hot-particle effects, results presented also apply to partial-organ or partial-tissue irradiation by any radiation source including external beams (e.g., electrons, neutrons, protons, heavy ions, and X-ray and gamma-ray photons).

Animals↗
PubMed1995

Models for estimating the risk of ulcers in the small intestine after localized single or fractionated irradiation.

Subacute and chronic ulcerations of the intestinal mucosa are important causes of serious complications following radiation therapy for abdominal or pelvic tumours. We describe dose-response models for estimating the risk of mucosal ulcers in the small intestine after uniform, localized single or fractionated (once-daily) X-ray exposure. The models were fitted to data for ulceration incidence, based on a 26 week post-irradiation follow-up of male Sprague-Dawley rats which received a wide range of single and fractionated once-daily 250 kV X-ray doses to a short loop (partial volume) of transposed, but functionally intact, small intestine. The models presented for single (Weibull (W)) and fractionated (modified Weibull (MW)) exposures of a partial volume of tissue allow estimation of the risk of radiation-induced injury. While the W model is not new, its adaptation to partial volume irradiation and the MW model are. Isoeffect relationships are presented for the uniform fractional dose Ds(i%) associated with an i% (e.g. 0%, 5%, 10%, 50%) risk of intestinal mucosal ulcers as a function of the number of once-daily dose fractions, where Ds(0%) represents the threshold fractional dose. Although the Ds(5%) and Ds(0%) estimates provided for intestinal mucosal ulcers are based on animal data, the ratio Ds(0%)/Ds(5%) and more generally ratios Ds(j%)/Ds(i%) (where i not equal to j), are presumed to apply to humans. The indicated ratios are predicted to be independent of the partial volume irradiated and the number of once-daily dose fractions, and may be independent of radiation quality. Isoeffect equations are also presented that apply to circumstances where different partial volumes within the same reference volume (i.e. the total volume of tissue considered) receive different doses, but the dose within a given partial volume is uniformly distributed. These isoeffect equations provide a means of converting non-uniform dose within a reference volume to uniform isoeffect dose to the total reference volume and may have applications outside the field of radiation therapy (e.g. evaluating effects of non-uniform exposure of the small intestine or skin by a hot particle).

Abdominal Neoplasms↗