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Biomedical subjects

G N Taylor

Publications and source records attributed to G N Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1995

Fission fragment relative biological effectiveness for liver tumor induction.

The risk coefficients for liver tumors as derived from 60 beagles with body burdens of 249Cf or 252Cf were used to determine the relative biological effectiveness of fission fragments relative to alpha particles. For liver malignancies the relative biological effectiveness was calculated to be about 2 +/- 3. The estimate based on the combined benign and malignant liver tumors was about 7, with a proportionately larger standard deviation of about +/- 14. Although the confidence intervals were wide, it is possible that the relative biological effectiveness of fission fragments relative to alpha particles, using liver neoplasia as the endpoint, is greater than 1.0 as compared to a value only slightly above zero when bone cancer was the lesion of interest.

Alpha Particles↗
PubMed1995

Soft tissue tumors among beagles injected with 90Sr, 228Ra, OR 228Th.

The occurrence of soft-tissue tumors in beagles given 90Sr (88 dogs), 228Ra (76 dogs), or 228Th (81 dogs) as young adults and followed throughout their lifespans was compared with that of 133 control beagles given no radioactivity. For animals injected with 228Ra, tumors of the eye were more prominent (p < 0.05) than in the controls, and soft-tissue tumors of cavities in the head (excluding the brain, mouth, and eye) were more prominent in dogs given 90Sr than in the controls (p < 0.05). There was some indication that eye tumors in animals given about 0.56 kBq 228Th kg-1 were associated with their radionuclide exposure. For tumors at a few other locations, the relative occurrence was greater (p < 0.05) in the controls. These included malignant tumors of the testis and malignant plus benign tumors of the mammae and vagina in 228Th dogs; both malignant and malignant plus benign tumors of the mouth and testis, and malignant plus benign tumors of the mammae and vagina in 228Ra dogs; and malignant plus benign tumors of the mammae in 90Sr dogs (p > 0.05 by Odds Ratio Chi Square analysis but p < 0.05 by Fisher's Exact Test). Differences in relative occurrence between radioactive dogs and controls of all other tumor types that appeared in any of the animals (notably lymphosarcoma, lymph node tumors, leukemia, mast cell tumors, liver tumors, etc.) were not statistically significant (p > 0.05). Intercurrent mortality, mainly from bone cancer, was higher in the radioactive dogs than in the controls. Mean survival was reduced in the dogs given 90Sr, 228Ra, or 228Th (13.17 +/- 2.64 y in controls, 10.95 +/- 4.06 y in 90Sr dogs, 9.07 +/- 3.61 y in 228Ra dogs, and 9.20 +/- 4.15 y in 228Th dogs). Attenuated lifespans could account, at least in part, for the relative paucity of soft-tissue tumors not induced by radiation among the groups of dogs given radioactivity and occurring near the end of life for control animals.

Animals↗
PubMed1995

Mammary tumor occurrence in beagles given 239Pu.

Comparison of 120 young adult female beagles given 0.026 to 106 kBq 239Pu kg-1 by intravenous injection and 63 comparable female control beagles showed that there were no significant differences in the risk of mammary tumor appearance between the two groups. This was the case for benign tumors only, for malignant tumors only, and for both malignant and benign tumors considered together. For malignant tumors the observed number was 73 as compared with 69 expected; for benign tumors, there were 131 observed and 126 expected; for all tumors (separate analysis, not just the addition of malignant plus benign), there were 199 observed and 199 expected. Chi-square analysis indicated that the p values for all these comparisons were > 0.05. There were 45 controls (71.4%) with any tumor vs. 67 dogs (55.8%) given Pu (95% C. I. = 46.9% to 86.2%). No significant differences could be established (Kaplan-Meier analysis) between these two groups for survival age at diagnosis of the first mammary tumor, 11.75 +/- 0.30 y for dogs given Pu vs. 11.90 +/- 0.36 y for controls. We reported previously that differences in mammary cancer occurrence had been identified between this same group of control dogs and 57 female beagles given 226Ra as young adults. The present study appears to support the earlier conclusion that something other than alpha irradiation of the skeleton (both 226Ra and 239Pu deposit in bone) seems to affect the appearance of mammary cancers, since internally deposited 226Ra does appear to induce these malignancies, possibly from initial deposition in mammary tissue of the parent radionuclide or the subsequent concentration in sensitive tissue of its radioactive progeny, 22Rn or isotopes of polonium, lead, and bismuth, which are absent in the case of 239Pu.

Animals↗
PubMed1995

Soft tissue tumors induced by monomeric 239Pu.

Individual records of soft tissue tumor occurrence (lifetime incidence) among 236 beagles injected with 239Pu citrate as young adults and 131 comparable control beagles given no radioactivity enabled us to analyze the possible effects on soft tissue tumor induction resulting from internal exposure to 239Pu. A significant trend was identified in the proportion of animals having malignant liver tumors with increasing radiation dose from 239Pu. There was also a significant difference in the relative numbers of both malignant liver tumors (3.2 expected, 22 observed) and benign liver tumors (18.1 expected, 66 observed). Malignant tumors of the mouth, pancreas, and skin were more frequent among controls than among the dogs given 239Pu as were all tumors (malignant plus benign) of the mouth, pancreas, testis, and vagina. For all other tumor sites or types, there was no significant difference for both malignant and all (malignant plus benign) tumors. Mammary tumor occurrence appeared not to be associated with 239Pu incorporation. We conclude that the only soft-tissue neoplasia induced by the intake of 239Pu directly into blood is probably a liver tumor.

Age Factors↗
PubMed1994

Skeletal malignancies among beagles injected with 241Am.

Seventy skeletal malignancies in 44 dogs were identified among 117 beagles injected as young adults with graded dosages of approximately 0.07 to 104 kBq 241Am kg-1 and maintained for lifetime observation. All of these tumors were osteosarcomas except four fibrosarcomas of bone and four chondrosarcomas of bone. Of these 117 animals, 114 survived beyond the minimum age (of 2.79 y) for radiation-induced bone cancer, and all are now dead. An expression was derived that described the dependence of percent occurrence of bone sarcoma on skeletal radiation dose of A = 0.76 + 30D, where A = percent of dogs with skeletal malignancy within any dosage group, D = average skeletal dose (< 3 Gy) at 1 y before death (average skeletal dose was calculated to the presumed start of tumor growth, which we have taken to be 1 y before death), and 0.76 represents the lifetime percent malignant bone tumor response among 132 suitable control dogs in our colony not given any radioactivity. All dosage groups with skeletal doses of > 3 Gy at 1 y before death exhibited close to 100% occurrence and appeared to be beyond the region of linearity. Therefore, they were excluded from the derivation of this expression. Similar analysis of corresponding data for beagles given 226Ra as young adults, excluding the two highest dosage groups in which the bone tumor response was approximately 100%, yielded the expression, A = 0.76 + 4.7D, (D < 20 Gy). A ratio of the coefficients in these two expressions indicates the effectiveness at low radiation doses for bone-cancer induction of 241Am relative to 226Ra, or (30 +/- 2.6)(4.7 +/- 0.47)-1 = 6 +/- 0.8. This compares to the relative effectiveness at low radiation doses that was obtained earlier for a 239Pu:226Ra toxicity ratio of about 16 +/- 5.

Americium↗
PubMed1994

Soft-tissue tumors among beagles injected with 226Ra.

A total of 409 primary soft-tissue tumors (189 malignant) occurred among 87 of 120 young adult beagles (72.5%) injected with 226Ra in eight dose levels ranging from 0.2-440 kBq kg-1 body mass, while a total of 565 primary soft-tissue tumors (208 of them malignant) were seen among 117 of 133 control beagles not given radioactivity (88%). Because the p-value for the difference in these two percentages was > 0.05, further comparisons were not made of all tumor locations or types taken together but only of the individual tumor locations or types. There was a clear excess of malignant tumors and all tumors (benign plus malignant) in the eye among dogs injected with radium (p < 0.05, p < 0.01, respectively), but the occurrence of all the other types of soft-tissue tumors was not greater in irradiated vs. control dogs (p > 0.05). This was also true for hematopoietic tumor types (including just one leukemia in a control and none in irradiated dogs) in which there was no difference between controls and dogs given radium. The following total tumors (benign plus malignant) occurred in control dogs but not in radium dogs: brain = 3, peritoneum = 1, and pituitary = 4. Malignant tumors other than leukemia appearing in control animals and not among radium dogs were brain = 2, lymph nodes = 1, adrenal = 3, uterus = 1, and pancreas = 5. Tumors that occurred in dogs given radium and not in controls were 3 mast cell sarcomas and 2 tumors of the thymus (1 malignant). Age at first tumor diagnosis for corresponding tumor types did not seem to differ (p > 0.10 or p > 0.05) between radium dogs and controls except for the eye (p < 0.05), with radium dogs being somewhat younger than controls at first diagnosis, at death, or at loss from the colony. Cox regression indicated differences between radium dogs and controls in risk of dying with specific tumors. The following tumors had p values of < 0.05 and risk ratios of > 2.2:eye, mouth (mostly melanomas), and thyroid for malignant tumors and for malignant and benign tumors together. When all sarcomas were considered as a group, there was no difference between controls and radium dogs but there was a difference for all carcinomas taken together, even when mammary tumors and eye tumors were excluded and when eye tumors alone were excluded.

Animals↗
PubMed1994

Occurrence of metastases in beagles with skeletal malignancies induced by internal irradiation.

Metastases from malignant bone tumors often are responsible for the fatal effects of these cancers. Characteristics of primary skeletal malignancies in beagles injected with bone-seeking radionuclides were studied by Thurman (1971) and summarized by Thurman et al. (1971). There were 212 tumors in 186 of these dogs for which we subsequently received information on bone tumor metastases. Evaluation of bone and soft tissue slides from these animals allowed us to compare parameters reported previously with the occurrence of grossly apparent bone tumor metastases. Data included growth-rate of the primary tumor, volume of the primary tumor at death, sex of the animal, growth period of the primary tumor, degree of calcification of the primary tumor, skeletal location of the primary tumor, cumulative radiation dose to the skeleton, dose equivalent to the skeleton, and year of death. For most of the comparisons, no significant differences could be established between dogs with and without metastases. However, tumor volume at death appeared to be correlated with probability of metastasis (p < 0.05), with the larger tumors being associated with higher rates of metastasis. Comparisons of dogs with and without metastases as a function of tumor growth-rate did not, for the most part, yield significantly different results between groups. Exceptions were when only one tumor per dog was considered for animals with multiple primary tumors and when only the tumor with the longest doubling time was included for all dogs with multiple primary tumors (p < 0.02). This effect was a result of only two tumors with doubling times > 45 d. Both had been characterized by Thurman (1971) as among the tumors with the least uncertainty in calculated doubling times. Rates of metastasis in dogs with primary tumors in paired bones were significantly higher than corresponding values of dogs with primary tumors in unpaired bones. Metastases in dogs with primary tumors in the ribs appeared to be more pronounced and those in the thoracic vertebrae appeared to be less pronounced than for animals with primary tumors in other bones as compared with the average for the whole skeleton.

Animals↗
PubMed1994

Eye tumors and other lesions among beagles given 90Sr or 226Ra.

Analysis of eye tumors and other eye lesions among beagles given either 90Sr or 226Ra, and among control animals, indicated that intraocular tumors in excess of the rate for our control animals were not associated with radiation from incorporated 90Sr + 90Y. It is unequivocal that eye melanomas were produced by injected 226Ra. Intraocular neoplasia, hyperplasia, hyperpigmentation, and melanosis in the eye all occurred in our control beagles given no radioactivity; however, tumor experience as currently reported for different beagle colonies may not be directly comparable because of differing rates of discovery, nonuniform nomenclature, and varying criteria for classification of lesions with their discordant interpretation by different pathologists.

Animals↗
PubMed1994

Distribution of skeletal malignancies in beagles injected with 239Pu citrate.

The distribution of skeletal malignancies among our beagles injected with 239Pu as young adults roughly seems to follow the distribution of skeletal mass and skeletal 239Pu. These findings are similar to those we reported previously for a group of dogs given 26Ra. Although there were differences in tumor distribution between the animals given 226Ra and those given 239Pu, most of them were not statistically significant; however, the radium dogs seemed to show a greater sensitivity to bone tumor origin in the tibia, while there may have been a tendency among the plutonium dogs toward increased relative sensitivity in the scapula, lumbar vertebrae, sacrum, and ribs. In contrast, the most common site for the formation of naturally-occurring bone malignancy in the dog is the distal radius. Perhaps there were too few tumors and too few dogs to establish statistical significance. A correlation between tumor location and at least two anatomical-physiological factors in the skeleton indicated that these two factors (site-specific bone turnover rate and percent of red marrow at the site, which is correlated with vascularity) may influence the appearance of malignancies both individually and in combination. Except for the femur, there appeared to be no difference between the relative distribution of skeletal malignancies of low-level (30 Bq-2 Bq kg-1 injected) and high-level (3-122 kBq kg-1) dogs. Distribution of bone tumors between the axial and appendicular skeleton was 50% vs. 50% for 239Pu (42 and 42), but it was 39% axial vs. 61% appendicular (22 and 35, respectively) for dogs given 226Ra. This difference was not significant (p > 0.2).

Animals↗
PubMed1994

Relative effectiveness of 239Pu and some other internal emitters for bone cancer induction in beagles.

The toxicity ratio (relative effectiveness per gray of average skeletal dose) has been estimated for bone cancer induction in beagles injected as young adults for a number of bone-seeking internal emitters. These experiments yielded calculated toxicity ratios (+/- SD) relative to 226Ra = 1.0 of 239Pu = 16 +/- 5 (single exposure to monomeric Pu) and 32 +/- 10 (continuous exposure from an extraskeletal deposit in the body), 224Ra = 16 +/- 5 (chronic exposure) and approximately 6 +/- 2 (single exposure), 228Th = 8.5 +/- 2.3, 241Am = 6 +/- 0.8, 228Ra = 2.0 +/- 0.5, 249Cf = 6 +/- 3, 252Cf = 4 +/- 2, 90Sr = 1.0 +/- 0.5 (for high doses) and 0.05 +/- 0.03 (for low doses) and 0.01 +/- 0.01 (for extremely low doses). Because no skeletal malignancies were observed among beagles given only 253Es, the toxicity ratio is undefined.

Animals↗
PubMed1994

Occurrence of mammary tumors in beagles given radium-226.

A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given 226Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon-->polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. Results of this study are potentially useful in understanding risks of radium-induced breast cancers in humans.

Age Factors↗
PubMed1993

Bone cancer occurrence among beagles given 239Pu as young adults.

The occurrence of skeletal malignancies has been documented among 234 young adult beagles given single intravenous injections of monomeric 239Pu citrate. Occurrence has also been documented among 132 comparable control group animals surviving the minimum latent time period of 2.79 y for radiation-induced bone cancer, who were maintained for lifespan observation. Injected amounts ranged from about 0.02-106 kBq kg-1 body mass with factors of 2 or 3 between dose levels. There were 84 radiographically apparent bone tumors in 76 plutonium-injected dogs and one tumor in a control group dog. Most of these were osteosarcomas except for seven chondrosarcomas, one liposarcoma, and one plasma cell myeloma of bone. The relationship between percent of dogs at any dose level with bone malignancy and average skeletal dose at the presumed time of tumor initiation of 1 y before death appeared to be linear below about 1.3 Gy average skeletal dose. The observed data can be approximated by the expression A = 0.76 + 75 D, where A = percent of dogs with bone cancer at any dose level, D = average skeletal dose in Gy (for doses up to 1.3 Gy) at tumor initiation, and 0.76 represents the percent tumor response in the control animals not given plutonium. Similar analysis of our corresponding data for beagles given 226Ra, excluding the two highest dose levels (approximately 100% occurrence), yielded the expression A = 0.76 + 4.7 D, where D = the average skeletal dose in Gy (for doses up to 20 Gy) at 1 y before death. The ratio of coefficients indicates the effectiveness for bone cancer induction of 239Pu relative to 226Ra, or [(75 +/- 22.5)(4.7 +/- 0.47)-1] = 16 +/- 5 for a single, brief intake of either nuclide into blood.

Animals↗
PubMed1993

Liver cancer induction by 239Pu, 241Am, and thorotrast in the grasshopper mouse, Onychomys leukogaster.

Forty young adult grasshopper mice (Onychomys leukogaster) of both genders were injected with either 129 or 44 kBq kg-1 of monomeric 239Pu and were maintained for lifetime observation. Average liver doses to death (mean times +/- standard deviation (SD) from injection to death = 405 +/- 133 and 756 +/- 189 d) were calculated as approximately 16 and 9 Gy, respectively. These animals developed a total of 18 primary liver tumors (neoplasms, malignant, and benign). Comparison of these mice to a previously published study involving 49 control animals of the same species, 70 mice given 241Am, and 73 given Thorotrast, indicated that the liver cancer induction of Thorotrast can be attributed almost exclusively to the effects of the radioactivity and not to its nonradiation properties. This suggests that projected risks of liver cancer induction from 239Pu, 241Am, or other liver-seeking actinides in humans probably can be estimated from the liver cancer experience in Thorotrast patients using the calculated radiation doses to liver. For this species, the linear risk coefficient for induction of liver neoplasia (percent of mice with liver tumor) by 241Am or Thorotrast was estimated to be about 14.6 +/- 5.4 times the average liver dose (in Gy) for groups of animals with average liver doses of 5 Gy or less. The lowest average liver dose among groups of these mice given 239Pu was about 9 Gy, the dose was not in the linear range, and it was too high to yield reliable results for determining a risk coefficient for low dose irradiation. However, the estimates for a risk coefficient were similar for the plutonium and americium mice with liver doses of approximately 9 Gy or 16 Gy.

Americium↗
PubMed1993

241Am-induced thyroid lesions in the beagle.

One of the features of 241Am metabolism in the beagle dog is a relatively high selective deposition in the thyroid glands, equal to approximately 0.06% of the injected dosage per gram. Retention is prolonged and principally in the interstitial connective tissue. The resulting average dose to the thyroid glands is about 1.42 and 0.76 times that delivered to the skeleton and the liver, respectively. This thyroid dose is much higher than has been reported in people. Although significant morphological changes and reductions in serum thyroxine occurred in this experiment, a significant increase in thyroid neoplasia was not observed.

Americium↗
PubMed1992

Strontium-90 induced bone tumours in beagle dogs: effects of route of exposure and dose rate.

Bone tumours from beagles exposed by inhalation to 90SrCl2 at the Inhalation Toxicology Research Institute (ITRI), by chronic ingestion of 90Sr at the Laboratory of Energy-Related Health Research (LEHR), and by injection of 90Sr citrate at the University of Utah were analysed to determine if the bone tumour characteristics differed among the three studies. The range of average skeletal doses at which the bone tumours occurred was similar in all three studies, but differences in the skeletal distribution, histological phenotype, and time to death were observed. The differences observed were attributed to the difference in dose-rate pattern obtained in the chronic ingestion study, in contrast to the inhalation and injection studies. In general, however, the differences noted in bone tumour characteristics were subtle, and would be unlikely to make an impact on models developed to assess the risk of human exposure to 90Sr.

Administration, Inhalation↗
PubMed1992

Promotion of radiation-induced liver neoplasia by ethanol.

The risk of americium-induced liver cancer in beagle dogs that received long-term dietary ethanol was two to three times that of their nonalcoholic cohorts, even though the radionuclide retention time in hepatic tissue was shortened by the alcohol treatment. Liver malignancies did not occur in the ethanol-treated, nonirradiated controls. An ethanol-induced tumor-promoting effect was not observed in organs or tissues other than the liver.

Americium↗
PubMed1991

Effectiveness of DTPA treatments following the injection of particulate plutonium.

A limited long-term experiment has been completed in which the chronic toxicity resulting from a single intravenous injection of 31.4 kBq of a poly-disperse 239Pu colloid sol per kg of body weight was tested in Beagle dogs. The Pu deposited mostly in the phagocytic cells of liver, spleen and to a lesser degree in lung and bone marrow. Slow solubilization of the Pu particles by endogenous ligands caused translocation of the nuclide and redeposition mostly as monomeric Pu in the skeleton and in liver hepatocytes. Thus, the deposit behaved as expected from a pulmonary or wound contamination in humans with a moderately soluble depot of Pu such as Class W hot particles. Therefore, this type of deposit provided the basis for a practical model to study the ensuing radiation effects under various experimental conditions. The dogs were divided into three groups of four animals each, and the following conditions were applied: (a) no further treatment was given, allowing free translocation of the Pu to its secondary deposition sites; (b) interception of the Pu translocation by weekly injections of 30 mumol of Ca-DTPA/kg of body weight (Ca-chelate of diethylene-triaminepentaacetic acid); and (c) interception of translocation by daily injections of 30 mumol/kg body weight of Zn-DTPA. For each of the groups (b) and (c), three dogs were used in a lifetime study, and one was sacrificed for nuclide distribution studies. Free translocation and subsequent deposition in the skeleton resulted in the death of each of the non-chelated dogs from osteosarcoma between 1267 and 1594 days after injection. Weekly treatment with Ca-DTPA reduced the total Pu burden significantly, but these dogs also died with osteosarcoma between 1462 and 1783 days. Daily injections with Zn-DTPA reduced the total Pu burden more efficiently than Ca-DTPA and prevented continuous deposition of solubilized Pu on bone surfaces. The mean post-injection survival of these dogs was 3520 days or about 2.1 times that of the animals receiving Ca-DTPA, while the latent period for bone tumour induction was about 2.6 times longer. This treatment reduced the severity of liver lesions and eliminated the occurrence of persistent leukopenia, but it did not prevent the formation of bone cancer.

Animals↗