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Biomedical subjects

E Polig

Publications and source records attributed to E Polig.

At least 19 recordsLinked to original sources

Biokinetic and dosimetric model of plutonium in the dog.

A biokinetic model of the systemic distribution and dosimetry of 239Pu in the beagle dog is presented. To achieve maximum consistency with experimental data, known histomorphometric parameters and results of autoradiographic studies were adopted directly. The remaining parameters were determined from retention and excretion measurements by optimization procedures. The beagle model attempts to parallel the human model as much as possible, but only one liver compartment and one compartment representing other soft tissues were needed to describe the data adequately. The salient features and differences of the biokinetic behavior of 239Pu beagles and humans are compared. Generally the organ retention of the beagle in relation to the lifetime is longer than in humans. This is particularly pronounced in the skeleton. Trabecular deposits of plutonium are gradually shifted to cortical sites. For the dosimetric model some additional features disregarded in the human model were employed. These relate to bone volume labels, a gradation of concentrations in marrow, the energy-dependence of absorbed fractions, and the self-absorption in marrow. The model predicts that the contribution of surface deposits to the endosteal dose still exceeds the contributions from bone volume and marrow labels. The average endosteal dose is about eight times and the marrow dose about two times larger than the average skeletal dose. The model provides the basis for the analysis of survival and relative risks.

Animals↗

Verification and modification of the ICRP-67 model for plutonium dose calculation.

On the basis of the available data and empirical expressions for the plutonium excretion after injection, an age-related compartmental model has been developed. It provides a better agreement with measured urinary excretion data than the current ICRP 67 model. Moreover, the revised model avoids unphysiological assumptions such as the transfer of activity from soft tissue to urinary bladder, that were part of the ICRP model. The new predictions of the activity in feces and in blood after an injection are closer to the available data than the ICRP 67 estimations and there is also a good agreement with the partitioning of plutonium between skeleton and liver obtained from different autopsy studies. Furthermore, the urinary excretion estimated by the improved model has been checked using some data from occupationally exposed individuals. As the plutonium uptake in these workers occurred by inhalation, the improved model and the ICRP 67 model were compared by connecting them to the ICRP 66 respiratory tract model. The improved model consistently yields a better agreement with the measured excretion and higher estimations of intake than the ICRP 67 model.

Body Burden↗

Microdistribution of 239Pu in the beagle skeleton.

The microdistribution of 239Pu was analyzed in the humerus, lumbar vertebra, and proximal ulna of young adult beagles using neutron induced autoradiography. The animals were sacrificed serially in groups of three at 4, 8, 16, 32, and 64 wk after a single injection of 3.5 kBq kg(-1) body weight. The kinetic behavior of surface concentrations was modeled using a simple concept of deposition and clearance in skeletal regions. Bones with high turnover showed a larger initial uptake and a faster clearance than bones with low turnover rates. Using a regression procedure, the surface deposition and clearance of plutonium was calculated as a function of the turnover rate. With time after injection the initial nonuniformity of trabecular surface labels tends to become more uniform. The trabecular:cortical affinity ratio is about 10. Trabecular activity is gradually translocated to cortical sites. The affinity ratio of forming to resting surfaces is about three. In some bones a continuous increase of marrow stars was observed, whereas in other bones no clear-cut tendency could be seen. The highest level of marrow labeling occurred in the lumbar vertebra and the humerus shaft.

Animals↗

Do cells repair precancerous lesions induced by radiation?

The most widely accepted point of view is that cells are endowed with the capacity to repair the primary lesions responsible for cancer induction. In radiobiology, this popular belief evolved from experiments of the same type as those that suggested the existence of sublethal radiation damage repair. The central problem with such data is that the cell-killing component of radiation damage may mask the effects associated with repair of precancerous lesions. The challenge is to separate the two processes that contribute to the observed tumor incidence after irradiation. using a recently developed stochastic model of radiation carcinogenesis allowing for cell death, we provide evidence that precancerous lesions are not subject to repair under certain experimental conditions.

Animals↗

Labels of surface-seeking radionuclides in the human skeleton.

A biokinetic model of the distribution and generation of skeletal labels of 239Pu in the human body is presented. The model is based on available information on the microdistribution of transuranics elements in animals and humans. It also makes use of morphometric and histomorphometric data characterizing the human skeleton and its turnover. The model correctly describes essential features of the microdistribution established from autoradiographic analyses. Calculated concentrations of skeletal labels of 239Pu are in good agreement with measurements from a human injection case.

Animals↗

A diversity of responses displayed by a stochastic model of radiation carcinogenesis allowing for cell death.

A stochastic model is presented of carcinogenesis induced by irradiation with arbitrary time-dependent dose rate. The key feature of the model is that it allows for radiation-induced cell killing to compete with the process of tumor promotion. Two versions of the model arise when considering target tissues with slow and rapid replacement of damaged cells. These versions show dissimilar shapes of the dose-response curves in the case of short-term exposure. The model provides a natural explanation of the basic experimental findings documented in the radiobiological literature.

Animals↗

Uranium skeletal dosimetry and distribution in young adult beagles: a guide for calculating uranium skeletal doses in humans.

Uranium isotopes were given via single intravenous injection into 22 young adult beagle dogs of both sexes to determine the metabolism of this element. Animals were given either 232U, 233U, 238U, or a combination of 232 (+) 233U. Calculations to assign a value of skeletal dose for each dog were performed using published radioactive properties of each uranium isotope and the metabolic data (including measured retention and skeletal distribution) derived from this study during a period of up to 2 y after injection. We believe that the procedures illustrated in this communication can serve as a useful pattern for estimating skeletal radiation doses to humans contaminated with 232U, 233U, or 238U.

Animals↗

Hits to bone cell nuclei from nonuniform radioactive labels.

The stochastic aspects of alpha-particle traversals through nuclei of bone-lining cells from nonuniform radioactive labels are worked out. Both the residence time of the target and the hit rate are considered random variables. It is shown that with any type of bone remodeling the fraction of cells not hit increases with increasing nonuniformity of the label concentration. Thus, a completely uniform concentration represents the most dangerous situation. A possible negative correlation between residence times and hit rates, observed in some experiments, tends to decrease the probability of alpha-particle hits. As a practical application, the theory is applied to the International Commission on Radiological Protection model of the distribution of 239Pu in the human body. In the case of 50 years of chronic ingestion of 1 annual limit of intake (ALI) per year for class W and chronic inhalation of 1 ALI/year for class Y compounds, more than 19.4 and 8.5% of the nuclei of bone-lining cells are traversed by at least one alpha-particle, respectively.

Alpha Particles↗

Statistics of hits to bone cell nuclei.

The statistics of hits to the nuclei of bone cells irradiated from alpha sources labeling bone tissue is described. It is shown that the law of remodeling of a bone structural unit (BSU), which describes the distribution of quiescence periods of this unit, affects the statistics of hits. It the irradiation of bone cells occurs during the whole cell cycle, the mean number of hits is independent of the law of remodeling. In this case the variance of hits has the minimum value for constant quiescence periods of BSUs (deterministic remodeling) and the maximum value for exponentially distributed quiescence periods (random remodeling). For the first generation of bone cells, i.e. for the cells which existed at the moment of the uptake of the nuclide, the mean number of hits depends on the law of remodeling. For random remodeling the mean number is equal to the mean value for the complete remodeling cycle. For deterministic remodeling the mean is only half this value. For the first generation of bone cells, changing the law of remodeling from random to deterministic increases the probability of no hits to the nuclei of bone cells. For the same mean value of hits, the difference does not exceed 13.3% of the total number of cells. For the subsequent generations of bone cells, such a change of the law of remodeling decreases the probability of no hits by 20.4%.

Alpha Particles↗

Local distribution and dosimetry of 226Ra in the trabecular skeleton of the beagle.

Young adult beagle dogs received a single injection of 38.1 kBq/kg body wt 226Ra and were serially sacrificed at 4 to 2955 days postinjection. Samples of sites of trabecular bone in the lumbar vertebral body, proximal ulna, and distal femoral metaphysis and epiphysis were analyzed autoradiographically. The time-dependent changes in the average 226Ra concentrations in the four regions were analyzed in terms of a compartmental model. The clearance rate from the lumbar vertebral body was about four times more rapid than for the proximal ulna and distal femoral epiphysis. Ratios of hotspot to diffuse label concentrations varied from about 10 to 23. The dose rate to the endosteum ranged between 8.7 and 39.5 mGy/day initially and 4 and 10.5 mGy/day toward the end of the observation period. Mean marrow dose rates were lower by a factor of 3 to 9.5. During their residence time the nuclei of bone lining cells receive a maximum dose of 8 Gy in the proximal ulna (2955 days after injection) and a minimum dose of 0.63 Gy in the lumbar vertebra (2955 days after injection). This corresponds on the average to 17 and 1.4 alpha-particle hits to the cell nuclei, respectively.

Animals↗

Hit rates and radiation doses to nuclei of bone lining cells from alpha-particle-emitting radionuclides.

Factors relating the local concentration of a bone-seeking alpha-particle emitter to the mean hit rate have been determined for nuclei of bone lining cells using a Monte Carlo procedure. Cell nuclei were approximated by oblate spheroids with dimensions and location taken from a previous histomorphometric study. The Monte Carlo simulation is applicable for planar and diffuse labels at plane or cylindrical bone surfaces. Additionally, the mean nuclear dose per hit, the dose mean per hit, the mean track segment length and its second moment, the percentage of stoppers, and the frequency distribution of the dose have been determined. Some basic features of the hit statistics for bone lining cells have been outlined, and the consequences of existing standards of radiation protection with regard to the hit frequency to cell nuclei are discussed.

Alpha Particles↗

A model of osteon closure in cortical bone.

A model of osteon closure is presented that incorporates some physiologic features of cortical bone remodeling, such as matrix synthesizing activity of osteoblasts, their burial as osteocytes, and elimination of cells. A simplified version of the model assumes a constant osteoblast activity throughout radial closure. An extended version allows for variable osteoblasts activity and is based on Lee's law of radial closure kinetics. The model calculations (extended model) show that both in humans and beagle dogs osteoblast activity steadily decreases during radial closure of the osteon. The potential of the model is also illustrated by calculating the dynamic change of the geometrical shape of the closing cone and the time dependence of the osteoid seam width, number of osteoblasts and bone formation rate in the closing cone.

Animals↗

Radiation dose factors for alpha-emitters in osteons and some considerations on dose non-uniformity ratios and relative distribution factors.

Dose factors for locations within a tissue-filled cylindrical cavity bounded by an infinite medium of bone labelled with an alpha-emitter are calculated by means of a Monte Carlo procedure. The calculational approach is general and allows us to determine dose factors for specific distances or target volumes defined by concentric cylinders, as well as various source geometries including surface sources, buried surface sources, infinite and bounded volume sources, and also comprises plane (trabecular) surfaces as a limiting case. Values for the dose factors and the contribution of cross-fire traversals are calculated mainly for 239Pu and 226Ra and a typical Haversian canal diameter of 30 microns in beagles and 70 microns in humans. Also tables are given that allow dose factors to be derived for the relevant range of alpha-particle energies, diameters and target distances. The dose non-uniformity factors (local dose rate/average skeletal dose rate) for 239Pu are 27.2 in humans and 14.0 in beagles. The corresponding values for 226Ra are in the ranges 1.18-1.26 (humans) and 0.90-0.97 (beagles) for a 222Rn retention between 10-30%. The relative distribution factors 239Pu/226Ra are 21.5-23.0 for humans and 14.5-15.6 for dogs. General expressions for calculating non-uniformity factors and relative distribution factors are derived and implications are discussed in the light of some experimental findings.

Alpha Particles↗

Kinetic model of the distribution of 239Pu in the beagle skeleton.

A model is presented to analyze the retention of Pu in the major deposition organs of the beagle dog and predict the dynamic behavior of skeletal labels. The kinetic part describing the gross organ distribution was represented by a compartment model. A fit to empirical retention equations of liver and skeleton yielded skeletal clearance corresponding to turnover rates of 93.8% y-1 and 3.8% y-1 in trabecular and cortical bone, respectively. Initially about 9% of skeletal Pu is deposited in cortical bone. The blood flow changes over a period of 3000 d from an initial 0.15% of the injected dose per day to 0.05% d-1 at the end of this period. More than 100% of the injected Pu is recirculated back to the skeleton during this interval. The calculation of the label dynamics showed that nearly complete volumization of Pu was only possible assuming a very high affinity ratio of forming vs. resting surfaces and high bone turnover rates. There was a steady increase in the fractional activity of surface and secondary diffuse labels in cortical bone whereas in trabecular bone these labels showed maximum activity at about 2 y after injection. The Pu concentration on pre-existing trabecular bone surfaces that were not remodeled within 3000 d post injection increased by a factor of 3.6. The model may be applied to single bones or the skeleton as a whole. The flow of Pu in the blood can be derived in human cases where urinary excretion rates are available. With the blood flow known, the model enables one to simulate the dynamic behavior of skeletal labels even for very general conditions of human contamination, including inhalation.

Animals↗

Bone structural parameters, dosimetry, and relative radiation risk in the beagle skeleton.

A variety of morphometric and histomorphometric parameters such as the mass of bone and marrow, bone surface areas, percentage of bone volume, percentage of the surface that is trabecular, and percentage of surfaces that are forming and resting are calculated for all major parts of the beagle skeleton. The total bone surface of the beagle is estimated at 2.9 m2 with 53.7% of the surface area being associated with trabecular bone. There are about 4.5 x 10(9) bone-lining cells and about 1 x 10(9) osteoblasts. From the fractional retention in each part of the skeleton, the initial surface concentration of 239Pu after a single injection of 592 Bq/kg body wt (0.016 microCi/kg) on resting surfaces and at sites of bone formation is calculated for various values of the affinity ratios of trabecular/cortical and forming/resting surfaces. These estimated concentrations then yield dose rates as well as cumulative and collective doses to bone-lining cells and osteoblasts in the different parts of the skeleton. On the assumption that the relative risk of tumor induction is proportional to the collective dose to either bone-lining cells or osteoblasts, the frequency of tumor occurrence is calculated and compared to observed frequencies. Both hypotheses yield approximate agreement with experimental data for different ratios of trabecular/cortical radiation sensitivity, although the differences between some bones are statistically significant.

Animals↗

Microdistribution and local dosimetry of 226Ra in trabecular bone of the beagle.

Sections of lumbar vertebral bodies of young adult beagle dogs have been analyzed autoradiographically to characterize and quantify the local distribution of 226Ra by means of a scanning microscope photometer. The animals received a single injection of 355 kBq/kg body weight and were serially sacrificed at 5 to 1381 days postinjection. Hotspot concentrations decreased from about 51 kBq/g bone at 5 days to 20 kBq/g at 1381 days postinjection. The diffuse concentration changed from 8.3 to 1.9 kBq/g. The mean 226Ra concentration in the trabecular areas scanned was initially higher and at the end of the observation period lower than the average calculated for the whole lumbar vertebral column. Density and area of, and fraction of bone activity in, hotspots virtually remained constant. With time hotspots tended to become translocated into bone volume. Mean dose rates to lining cells from both hotspots and diffuse labels decreased from about 210 mGy/d at early postinjection times to 105 mGy/d. This corresponds to 2.5 to 1.1 times the average skeletal dose rate. A discussion of the level of irradiation in terms of hit frequencies shows that osteoblasts in the initial phase of hotspot formation receive about 60 hits to their nucleus for the duration of bone formation. After about 6 months, however, the 226Ra concentration in new bone and the corresponding hit frequency appears to be low enough that interference with bone formation is unlikely. Morphometric measurements showed that abnormal bone accretion and thickening of trabeculae occurred. This was interpreted as an imbalance between bone formation and resorption. Both formation and resorption seem to be substantially lowered compared to control animals.

Animals↗

Bone age and remodeling: a mathematical treatise.

Remodeling of an element of mineralized bone is described by specifying the probability per unit time of being replaced as a function of age of the element. The functional dependence of this probability is called the "law of remodeling." The properties of this stochastic law of remodeling are discussed in terms of random, selective, and redundant remodeling. A relationship between the law of remodeling and the mean bone tissue age is derived. It is shown how the probability density of bone age for individual elements of bone depends on the law of remodeling. The mathematical formalism is exemplified by assuming a specific parametric form of the law. A procedure for experimentally determining the law is suggested based on tracing the resorption of single fluorescent labels. Finally, the extension of the model to a real skeleton with regional differences in turnover rates is discussed.

Age Determination by Skeleton↗