Observation of picometer vertical emittance with a vertical undulator.

Using a vertical undulator, picometer vertical electron beam emittances have been observed at the Australian Synchrotron storage ring. An APPLE-II type undulator was phased to produce a horizontal magnetic field, which creates a synchrotron radiation field that is very sensitive to the vertical electron beam emittance. The measured ratios of undulator spectral peak heights are evaluated by fitting to simulations of the apparatus. With this apparatus immediately available at most existing electron and positron storage rings, we find this to be an appropriate and novel vertical emittance diagnostic.

Synchrotron radiation hardness studies of PILATUS II.

A synchrotron beam has been used to investigate the radiation tolerance of a PILATUS II module. It has been demonstrated that radiation-induced threshold shifts become significant above 30 Mrad. Individual adjustment of pixel thresholds after irradiation enabled retention of standard behaviour in excess of 40 Mrad. This implies that a module can be continuously irradiated for in excess of 40 days at an individual pixel count rate of 10(6) counts s(-1).

Ancestry of beagles in lifespan studies of radionuclide toxicity at the University of Utah.

Analysis of the ancestry of the 1,262 lifespan beagles (LSB) entered into lifespan studies at the Radiobiology Division, University of Utah, beginning in 1952 and ending in 1980, indicated that about 97% of ancestor citations in the various pedigrees were of only 10 breeding animals (breeders) among breeders within the beagle colony. In turn, just 18 AKC-registered "champion" beagles from outside of this colony (founders) accounted for about 98% of all ancestor citations among founders for the LSB. We conclude from this study that the animals used in the lifespan radionuclide experiments can be considered to be somewhat genetically interrelated.

Search for a genetic link for mammary cancer in a beagle colony.

BACKGROUND: A possible genetic link for malignant mammary tumor (MMT) was investigated. MATERIALS AND METHODS: Records of an internally-irradiated beagle colony followed from the early 1950's until about 1995 were searched and analyzed by standard statistical procedures. RESULTS: Only a single ancestor yielded a "p" value (Fisher's Exact Test) for an overrepresentation among descendants with MMT at < 0.025 (one-sided test), and the number of comparisons for the 169 ancestors where the relative fraction of animals with MMT was greater than that for non MMT dogs (61) suggests that this could have occurred by chance alone. Results of other statistical tests were not remarkable. CONCLUSION: No genetic link for MMT in this colony could be established with the available data. These findings may or may not be relevant to humans.

Review of 239Pu and 226Ra effects in beagles.

A long term biological study has been completed that was designed to assess the predicted effects in humans of internally deposited 239Pu by comparison with 226Ra in beagles. Herein we summarize for the first time results of several previous reports about the effects of these two radionuclides in our beagles in an attempt to elucidate what has been learned since the beginning of the study in the early 1950's. Perhaps the most important finding was that bone surface-seeking plutonium is more toxic at equal mean skeletal radiation doses (<3 Gy for 239Pu, <20 Gy for 226Ra) than bone volume-seeking radium for the induction of skeletal malignancy by about a factor of 16 for a single intravenous injection of monomeric 239Pu. In addition, ancillary studies have shown that when plutonium transfers continuously onto bone surfaces from a depot of particulate 239Pu in phagocytic cells, its relative toxicity per Gy average skeletal dose is enhanced by about a factor of 2. Juvenile animals or dogs injected as mature adults were only about half as sensitive for equal mean skeletal doses as dogs injected as young adults. Male and female dogs were about equally sensitive to radiation of the skeleton by either radionuclide. Findings about radiation-induced fractures are summarized as well as data on the induction of soft-tissue malignancies by 239Pu or 226Ra. Natural survival was not affected at the lower dosage levels of either 226Ra or 239Pu as compared with control dogs given no radioactivity, but the survival of animals at higher levels was reduced. No additional life-shortening effects beyond those attributable to occurrence of radiation-induced malignancies or other radiation-induced effects were suggested by analysis of data for low dosage levels.

Does longevity in beagles injected with bone-seeking radionuclides depend upon radiation dose in the absence of known radiation effects?

Regression analyses of longevity as a function of skeletal radiation dose among groups of beagles injected with 226Ra, 228Ra, 228Th, 241Am, 90Sr or monomeric 239Pu suggested that at low doses and dose-rates (those at which induced effects are low), age at death seems to be independent of dose when animals dying with specific radiation effects were excluded, although longevity does appear to be a function of dose when animals dying with established radiation effects and at all doses were included. We conclude tentatively that, for mammals receiving skeletal dose from bone-seeking radionuclides at low doses and low dose-rates, longevity may not be dependent upon skeletal radiation dose in the absence of radiation-induced malignancies or other radiation effects.

Effective thresholds for induction of skeletal malignancies by radionuclides.

Our analysis of data from the beagle project completed at the University of Utah has provided some comparisons that appear to be useful in testing the model proposed by Raabe of effective thresholds for induction of skeletal malignancy by bone-seeking radionuclides in beagles. Raabe's model predicted that cumulative skeletal doses of less than about 0.9 to 1.4 Gy from alpha emitters or 28 to 70 Gy from beta emitters deposited in the skeleton require a long enough time for bone cancer expression that the dog's natural lifespan would be exceeded before the tumor appeared. Results from the Utah beagle project seem to confirm these projections for 226Ra, 228Ra and, perhaps, for 90Sr. The lowest doses at which malignant bone tumors were observed in animals injected with these radium isotopes were about 0.9 Gy (226Ra) and 3 Gy (228Ra). For the beta emitter, 90Sr, the lowest doses at which bone tumors were seen were about 18, 50, and 70 Gy with an expectation for naturally occurring tumor of about one. Twenty-six of the two hundred and thirty-three Utah beagles given monomeric 239Pu that developed skeletal malignancies had doses between 0.02 and 0.51 Gy (80 of these dogs had skeletal doses of less than 0.9 Gy). Three dogs of 54 given 241Am with doses lower than 0.9 Gy had bone tumors at 0.23, 0.56, and 0.88 Gy with the expectation of about one naturally occurring case. For 25 animals injected with 228Th at skeletal doses below 0.9 Gy, one bone tumor dog had a dose of about 0.4 Gy, and the expectation of a dog with natural tumor among the group was only about 0.38. Five beagles of 74 given 224Ra with resulting doses of less than 0.9 Gy died with skeletal malignancy at 0.32 Gy or less with an expectation for non 224Ra induced tumor of about one. It appears that Raabe's proposal might be confirmed for some but not all of the radionuclides used in the Utah studies. Models presented in earlier papers by Raabe provide results that are somewhat different from his recent abstract and compare more favorably with those cited herein for Utah dogs. Re-examination of our data for these analyses has suggested a novel concept for calculation of carcinogenic dose to endosteal bone surfaces.

Radium-induced eye melanomas in dogs.

The intraocular radiotoxicity of intravenously injected 226Ra and 228Ra was studied in beagle dogs. Approximately 0.071% of injected radium was retained in each eye of beagles following intravenous administration. The retention was principally in the tapetum and the intraocular pigmented structures where significant pigmentary lesions were produced. These included melanotic plaques on the iris, melanosis of the ciliary body, varying degrees of tapetal degeneration, and intraocular melanomas. The tumors occurred principally in the ciliary body and to a much lesser extent in the iris. They appeared to arise from the pigment epithelium layer of the ciliary body. Thus, unlike melanomas arising in other sites, they are apparently not of neural crest origin. In addition to bone cancer, they represent another radium-induced neoplasm in beagles. Radium-induced intraocular melanomas have not been reported in people.

Does body size contribute to sensitivity of bone tumor induction by radionuclide exposure?

Investigation of a possible increase in sensitivity to occurrence of radionuclide-induced skeletal malignancy with increasing body size was analyzed among 358 beagles injected as young adults with either 226Ra or monomeric 239Pu and maintained for their lifespans. Corresponding analyses were performed for about 240 other beagles injected as young adults with 90Sr, 228Ra, or 228Th. Body masses at the time of injection ranged between about 5.6 and 16 kg. Logistic regression analysis using body mass and cumulative skeletal radiation dose as the independent variables indicated that there could not be established a dependency of tumor occurrence upon body mass, although skeletal dose was found to be significantly correlated with occurrence of bone cancer. Regression analysis indicated that for any dosage group there could not be established a correlation between body mass and skeletal dose. Each dosage group having similar injected kBq kg(-1) for each nuclide was divided into 2 subgroups of equal size, one containing the less massive dogs and the other containing the more massive dogs. These subgroups within a roughly uniform value of skeletal dose-rate were compared by Fisher's Exact Test, and the less massive subgroups were combined within each nuclide for an additional, separate analysis against the combined more massive subgroups using the same method. In only one instance (the dosage group given 3607 kBq 90Sr kg(-1)) was there indicated a substantially greater tumor occurrence among dogs in the more massive subgroup (p = 0.061). However, for the group given 0.382 kBq 239Pu kg(-1) there was indicated a significant difference between subgroups, but the effect was exactly opposite to that found for the highest level 90Sr dogs in that the less massive subgroup had a higher relative tumor occurrence than the most massive (p = 0.042). For all groups with a p-value < 0.10, a possible correlation was investigated between survival and body mass at injection (since bone tumor occurrence might be a function of longevity), but a significant relationship could not be determined. No significant differences could be established between the combined more massive and the combined less massive subgroups for any radionuclide. We conclude that, for the conditions in our experiment, relative size within a species does not contribute importantly to the sensitivity (lifetime occurrence) for induction of skeletal malignancy.

Fracture occurrence from radionuclides in the skeleton.

Because skeletal fractures were an important finding among persons contaminated with 226Ra, experience with fractures among dogs in our colony was summarized to determine the projected significance for persons contaminated with bone-seeking radionuclides. Comparison by Fisher's Exact Test of lifetime fracture occurrence in the skeletons of beagles injected as young adults suggested that for animals given 226Ra, 228Ra, 228Th, or 239Pu citrate, there was probably an excess over controls in fractures of the ribs, leg bones, spinous processes, and pelvis (os coxae) plus the mandible for dogs given 226Ra and the scapulae for dogs given 228Ra or 228Th. Regression analysis indicated that significantly elevated fracture occurrence was especially notable at the higher radiation doses, at about 50 Gy average skeletal dose for 239Pu, 140 Gy for 226Ra, about 40 Gy for 228Ra, and more than 15 Gy for 228Th. The average number of fractures per dog was significantly elevated over that noted in controls for the highest radiation doses of 239Pu and 226Ra and for the higher doses of 228Ra and 228Th. For those dogs given 90Sr citrate, there was virtually no important difference from control beagles not given radionuclides, even at group mean cumulative skeletal radiation doses up to 101 Gy. Because of a large proportion of dogs with fractures that died with bone malignancy (even at dosage levels lower than those exhibiting an excess average number of fractures per dog), we conclude that fracture would not be an important endpoint at lower levels of plutonium contamination in humans such as would be expected to occur from occupational or environmental exposure.

Cases from the aerospace medicine residents' teaching file. Decompression sickness.

Decompression sickness is an uncommon but serious risk associated with flying and SCUBA diving with potential for significant morbidity and mortality. It can occur in both novice and experienced individuals. This case illustrates an atypical presentation of decompression sickness in an experienced amateur SCUBA diver. Clinical suspicion must be high, since the presenting symptoms can be nonspecific as in this case. Early recognition and treatment are important for maximum recovery.

Relative radiosensitivity of bone tumor induction among beagles as a function of age at injection of 239Pu or 226Ra.

A comparison was made of the response to induction of skeletal malignancy from exposure of beagles to monomeric 239Pu or to 226Ra as juveniles (3 mo of age), young adults (1.5 y of age), or mature adults (5 y of age). This indicated that of these age groups, animals injected as young adults are most sensitive per Gy of average skeletal dose evaluated at 1 y before death. Dogs exposed either as juveniles or as mature adults appeared to be less sensitive. Relative radiosensitivities (RRS) of juvenile and mature beagles ranged between about 0.3 and 0.7 that of dogs injected as young adults. Mean values of RRS for both radionuclides were about 0.5, but RRS values derived from dogs given monomeric 239Pu appeared to be most reliable and were 0.27+/-0.09 for dogs injected as juveniles and 0.41+/-0.13 for animals exposed as mature adults.

Is there a difference in radionuclide-induced bone tumor sensitivity between male and female beagles?

An analysis of bone tumor occurrences among male and female beagles given monomeric 239Pu or 226Ra was not able to establish a difference in sensitivity to induction of bone malignancy by radium or plutonium exposure. This is in contrast to the situation reported for mice. Female mice are substantially more sensitive to 239Pu irradiation than males, but this difference is obliterated by gonadectomy, females becoming less sensitive and males becoming more sensitive. Although there may be some nonuniformity between human males and females for radiation-induced bone sarcoma occurrence, analysis of data sets containing both men and women exposed to 224Ra, 226Ra, 228Ra, or 226+228Ra appears not to reveal substantial differences in sensitivity by gender, a situation similar to that reported herein for beagles.

241Am removal by DTPA vs. occurrence of skeletal malignancy.

Beagle dogs injected with 241Am and treated subsequently with DTPA exhibited a reduced occurrence of skeletal malignancies and increased lifespans when compared to corresponding untreated animals also given 241Am. Whereas 92% of dogs given about 11 kBq 241Am kg(-1) and not treated with DTPA developed bone cancer (skeletal dose about 5.9 Gy), skeletal malignancy was seen in only 40% and 27%, respectively, among two groups of DTPA-treated animals injected with 11 kBq kg(-1) (doses of 5.7 and 1.7 Gy). The median lifespan among the untreated dogs was 1,728 d, but the median lifespans in the DTPA-treated groups were 2,478 and 3,654 d, respectively. Untreated dogs with a skeletal dose averaging about 2 Gy had 53% bone cancer occurrence and a median lifespan of 3,227 d. These data did not enable us to address the question of whether the reduction in cancer occurrence was proportional to, greater than, or less than the reduction in skeletal dose, but the third possibility seems unlikely.

Does age of the host affect growth rates of skeletal malignancies?

Statistical analysis of bone tumor growth rates as a function of age at initiation of radiation-induced skeletal malignancies in our animal colony indicated that the p value for an association between these parameters was <0.05, suggesting a correlation in beagle dogs. The youngest animals appeared to exhibit the most slowly growing tumors, and the trend was toward more rapidly growing tumors with increasing age. Less effective immune systems in older animals were invoked as a possible explanation of this relationship.

Relationship of natural incidence and radiosensitivity for bone cancer in dogs.

A comparison of the risk coefficients for 239Pu- or 226Ra-induced bone cancer in two canine breeds, one with a relatively low (beagle) and the other with a very high (St. Bernard) natural incidence, indicated only slightly higher risk in the giant breed. The differences in risk for skeletal malignancy in 239Pu and 226Ra dogs were nonsignificant (p > 0.05). Likewise, the values of the 239Pu:226Ra "toxicity ratios" for these respective breeds, using bone cancer as the endpoint, were not significantly different at the 0.05 level. The anatomical distribution of the radiation-induced bone tumors tended to be a function of both the bone mass and the skeletal distribution of the radionuclide, not the site of predilection for naturally occurring bone neoplasia. Although the etiology of the higher natural incidence of bone cancer in the St. Bernard was not determined, several possible factors, including a higher osteoblastic activity level in the St. Bernards, are presented. These data suggest that making extrapolations of radiation-induced bone cancer risk from animals to humans is valid.

Bone tumor location in dogs given skeletal irradiation by 239Pu or 226Ra.

Statistical analyses have indicated that there was a significant difference between dogs injected with bone volume-seeking 226Ra as compared to those given bone surface-seeking 239Pu with respect to location within the skeleton of 334 radiation-induced primary bone malignancies. Corresponding differences also were evident when dogs given bone volume-seeking 90Sr or bone surface-seeking 241Am, 228Th, (249,252)Cf, or 224Ra (which decays mostly on bone surfaces because of its short, 3.6 d half time) were included along with the 226Ra or 239Pu, respectively (562 total tumors). Further analysis suggested that higher values of percent red marrow (M) and bone turnover rate (R) are correlated with increased probability of tumor appearance at a particular location within the skeleton for the surface seekers. Proportionately higher values of M and R are associated with skeletal sites containing mostly trabecular bone as compared to those with mostly compact (cortical) bone. Coefficients of determination (r2) for the relationship between percent of total tumors vs the combination of percent red marrow and turnover rate (= MR) was about 0.7 for the surface seekers but only about 0.1 for the volume seekers. This indicates that the neoplastic effects of surface seekers, but not volume seekers, are associated with the presence of trabecular bone at the various sites of radionuclide deposition within the skeleton.

Comparison of internal emitter radiobiology in animals and humans.

Investigations of radionuclide metabolism and effects in various mammalian species revealed important similarities between animals and humans and between some animal species. These include skeletal deposition of radium and radiostrontium in bone volume; deposition on bone surfaces of plutonium and other actinides; liver deposition of actinides; induction of skeletal or liver malignancies by these radionuclides; induction of tooth and jaw abnormalities; mammary cancer induction by radium in humans and in the beagle; depression of circulating cells in blood; and induction of bone fractures. There are also inter-species differences that may not have been noted if multiple species (including humans) had not been studied. Some of these are more rapid excretion of radium in humans compared with most other mammals; induction by radium of eye melanomas in animals but not humans; rapid loss of deposited plutonium from liver in many species of mice and rats but not in humans and dog; substantial sex-related differences in skeletal plutonium retention and bone sarcoma induction in mice but not in humans or dog; and induction of head sinus carcinomas by 226Ra in humans but not the beagle. Leukemia and other related neoplasms were not induced in radionuclide-injected lifespan dogs in excess of the occurrence in control animals. Much of our current understanding of skeletal biology and radionuclide behavior in mammals was derived from this and related projects. The primary goal of the Utah experiment of estimating toxicities of bone-seeking radionuclides relative to radium has been accomplished. For 226Ra = 1.0, comparative toxicities (ratios) of a single injection for bone tumor induction in beagles were about 16 +/- 5 for monomeric 239Pu (32 +/- 10 for chronic exposure), 6 +/- 0.8 for 241Am, 8.5 +/- 2.3 for 228Th, 6 +/- 3 for 249Cf, 4 +/- 2 for 252Cf, 6 +/- 2 for 224Ra (16 +/- 5 for 50 weekly injections), 2 +/- 0.5 for 228Ra, and between 0.01 +/- 0.01 and 1.0 +/- 0.5 for 90Sr, depending on the dose-rate, with the lowest dose-rates approaching a ratio of zero. Corresponding ratios in mice for 226Ra = 1.0 were 16 +/- 4 for monomeric 239Pu, 5.4 +/- 2.0 for 224Ra (16 for 50 weekly injections), 4.9 +/- 1.4 for 241Am, 5.0 +/- 1.4 for 249Cf, 2.6 +/- 0.8 for 252Cf, 4.4 +/- 1.8 for 243,244Cm and about 1.0 for 90Sr at high doses, decreasing to near zero for low doses.

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.