Charles W. Mays

Bone cancers induced by 224 Ra (Th X) in children and adults.

AbstractThe average skeletal dose in rads was calculated for 217 juveniles and 708 adults injected with 224Ra (mainly during the years 1946–1951) for the treatment of tuberculosis, ankylosing spondylitis and other diseases. We determined experimentally that for each 1000 esE stated by the supplier,

Leukemia risk from neutrons.

Abstract An analysis of the leukemia incidence in A-bomb survivors at Hiroshima and Nagasaki, which utilizes recently published depth dose calculations, discloses a substantial risk of leukemia induction by the maximum permissible annual dose equivalent for occupational exposure. The possibility that occupational exposure to neutrons may also pose a significant risk of induction of other neoplasms is considered. A reduction in the maximum permissible dose equivalent for neutrons seems indicated.

Cancer risk from the lifetime intake of Ra and U isotopes.

From extensive human data on the induction of skeletal cancers (bone sarcomas and carcinomas of the head sinuses) by 226Ra, 228Ra and 224Ra, the cumulative lifetime risk to 1 million people, each ingesting 5 pCi of a Ra isotope per day, was calculated to be nine bone sarcomas plus 12 head carcinomas for 226Ra, 22 bone sarcomas for 228Ra, and 1.6 bone sarcomas for 224Ra. Assuming that the risk per rad of average skeletal dose is equal for 226Ra and the U isotopes with half-lives exceeding 1000 yr and that the equilibrium skeletal content is 25 times the daily ingestion of 226Ra, but 11 times the daily ingestion of long-lived U, the cumulative life-span risk to 1 million persons, each ingesting 5 pCi per day of 233U, 234U, 235U, 236U or 238U, is estimated to be about 1.5 bone sarcomas. The U risk is not well established and additional research is needed on the metabolism of U in humans and its carcinogenicity in laboratory animals. These estimates assume linear dose responses. However, if incidence varies with the square of dose, virtually no induced cancers would be expected from these levels of radioactivity.

A Trophic Level Effect on 137cs Concentration

Abstract In many animal species, the cesium/potassium ratio in the body is about two to three times higher than the cesium/potassium ratio in their normal diets. Data indicate that this increase ratio is greater with increased potassium intake and is larger in adult humans than in children.

Comparative toxicity of 226Ra, 239Pu, 241Am, 249Cf, and 252Cf in C57BL/Do black and albino mice.

Groups of C57BL/Do (black and albino) mice were injected with graded activities of 226Ra, 239Pu, 241Am, 249Cf, or 252Cf and were followed throughout life. Bone sarcoma was the principal radiation-induced end point, and the risks associated with average skeletal doses of the four transuranium radionuclides, relative to radium, were determined. The relative biological effectiveness (RBE) was calculated for each emitter by dividing its risk coefficient (bone sarcomas per 10(6) mouse-rad) by the risk coefficient for 226Ra. Combined data for males and females in both black and albino mice gave the following values +/- SD for the RBE relative to 226Ra = 1.0: 239Pu = 15.3 +/- 3.9, 241Am = 4.9 +/- 1.4, 249Cf = 5.0 +/- 1.4, and 252Cf = 2.6 +/- 0.8. About 70% of the tumors occurred in the axial skeleton, and the risk coefficient for females averaged about four times higher than for males when all five nuclides were included. The RBE of fission fragment irradiation from 252Cf for cancer induction, relative to alpha irradiation, for the combined data in all of the animals given 252Cf and 249Cf, was 0.02 +/- 0.28, in agreement with the calculated theoretical value of 0.03, based on the ratio of summed track lengths in tissue.

Americium-241 studies in beagles.

Forty-eight adult beagles were injected with 0.00179 to 4.49 pCi 241Am/kg body mass. Retained activity in the living animals was evaluated via the 60 keV gamma-ray using a combination of total-body and partial-body counting to determine the proportion in the liver and in non-liver tissue. Soon after injection, about 50% and 40%, respectively, of the administered 241Am was deposited in the liver and non-liver tissue (mainly skeleton). In the animals injected with 0.00179-0.305 pCi/kg the liver and non-liver burdens decreased slowly each with a biological half-time of about 10 yr during the first 850 days. Two dogs injected with about 2.80 ,uCi/kg exhibited a sharp decrease in liver retention beginning about 100 days after injection accompanied by an increase in non-liver 241Am. Both showed extreme degenerative liver changes at death 401 and 448 days after injection. Similar but more slowly progressing effects were observed in the retention of 241Am by two animals injected with about 0.904pCi/kg. Excreta collections from four dogs during the first 3 weeks after injection showed that f of the excretion was urinary and that nearly 2 of the total z41Am excreted during this period appeared in the first day’s collection. Evaluation of the activity of individual bones, organs, and tissues of six animals autopsied 1-448 days after injection showed that although 241Am was distributed in many soft tissues, the liver and skeleton were the principal deposition sites; however, americium concentration in the thyroid gland was higher than in the skeleton and was higher than in any other soft tissue except the liver. Autoradiography showed that 2aArn was deposited close to the location of the functioning thyroid cells. The kidney also had a relatively high concentration of activity, selectively deposited in the glomeruli.

Plutonium- or americium-induced liver tumors and lesions in beagles

Plutonium-239 or 241Am administered intravenously in the monomeric citrate form was initially deposited in beagle livers principally in the hepatocytes and to a much lesser extent in the sinusoidal macrophages and connective tissues. The initial distribution was quite uniform throughout the hepatic parenchyma; however, at later postinjection intervals, depending on the amount of injected activity, the liver burden became increasingly more focal due to: (1) a progressive shift of the radionuclide from the hepatic epithelium to the macrophages; (2) the movement of such macrophages toward the portal or central regions of the lobule; and (3) the displacement of the older more radioactive tissue by regenerating hepatocytes, which generally have a much lower radionuclide content. The hepatic lesions produced by Pu or Am included: (1) necrosis and degenerative changes that were clinically serious or fatal in some of the animals injected with approximately 107 kBq kg-1; (2) marked structural and circulatory changes resulting from necrosis and focal hepatocyte hyperplasia; (3) a significant incidence of both benign and malignant primary liver tumors. In both Pu- and Am-treated dogs, the most frequently appearing neoplasm was the bile duct adenoma, followed by the cholangiocarcinoma. The most obvious difference between Pu- and Am-induced liver neoplasia was the greater frequency of fibrosarcomas and mast cell sarcomas in the Am-treated groups. Hepatomas were of relatively low frequency in animals with Pu or Am burdens. Although the incidence of bone neoplasia was high among the dogs in these studies, the risk of liver tumors, especially in the Am-treated animals, exceeded that of the skeleton in some of the lower dosage levels where the survival times were long. A risk coefficient of approximately 1200 fatal liver malignancies (10(4) beagle Gy)-1, derived from the dosage groups with long survival times, was calculated for combined Pu and Am animals. The prominence of the liver syndromes in beagles with burdens of Pu or Am indicates that humans with body burdens of 239Pu, 241Am, or other actinide elements may be at risk from radiation effects in the liver, including neoplasia development.

Skeletal Effects Following 224ra Injections Into Humans

Abstract Repeated injections of 224Ra into German patients have produced tooth breakage, growth retardation, benign exostoses, and malignant bone sarcomas. Tooth breakage was most frequent in adolescents 1120 yr old at 224Ra injection. Growth retardation and exostoses were most frequent in the very young children and were not induced in adults. Bone sarcomas have occurred in 54 of the 897 traced patients of known and unknown dose, with appearance times ranging from 3.5 to 22 yr after 1st 224Ra injection. For patients of known dose and injection span, bone sarcomas occurred in 35 of 204 juveniles (1110 rad average skeletal dose and 11 months average injection span), and in 13 of 612 adults (210 rad average skeletal dose and 6 months average injection span). For equal injection spans, the juveniles were only slightly more sensitive per rad than the adults to 224Ra-induced bone sarcomas. The incidence of bone sarcomas from a given dose of 224Ra increased as the span of the injection series increased, and this effect in humans has been confirmed in the Neuherberg mice.

Cancer induction in man from internal radioactivity.

The indicated malignancies have been induced in exposed persons by the following radionuclides and their decay products- /sup 222/Rnuranium miners -- lung carcinomas; /sup 226/Ra-- dial painters --bone sarcomas and sinus carcinomas; /sup 232/Th-- thorotrast cases -- liver cancers; /sup 224/Ra- German patients-- bone sarcomas; /sup 32/P -- polycythemia patients -leukemia; and /sup 131/I- Marshall Islanders- thyroid tumors. Each of these examples is discussed in turn. (auth)

Removal of Pu and Am from beagles and mice by 3,4,3-LICAM(C) or 3,4,3-LICAM(S)

Decorporation of Pu and Am by tetrameric catechoylamide (CAM) ligands has been investigated in beagles and mice. Eight dogs were injected intravenously (iv) with 237 + 239Pu(IV) + 241Am(III) citrate, and 30 min later, pairs of dogs were injected iv with 30 mumole/kg of 3,4,3-LICAM(C) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-5-sulfobenzoyl)tetr aazatetradecane, tetrasodium salt], 3,4,3-LICAM(S) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-4-carboxybenzoyl)te traazatetradecane, tetrasodium salt], CaNa3-DTPA, or each of the latter two ligands. Blood was sampled, and excreta were collected for 7 days, at which time the dogs were sacrificed and nuclide retention in liver and nonliver tissue was measured. Groups of five mice were each given 238Pu(IV) or 241Am(III) citrate iv; 3 min later 30 mumole/kg of a CAM ligand was injected intraperitoneally, mice were killed at 24 hr, and separated excreta and tissues were analyzed. In the dogs, average retention at 7 days of the injected Pu and Am, respectively, was as follows: 12 and 70% after treatment with a CAM ligand alone; 30 and 20% after DTPA; 12 and 20% after LICAM(S) plus DTPA; 90 and 89% without a ligand. In the mice, mean retention of the injected Pu and Am, respectively, was as follows: 14 and 66% after treatment with LICAM(C); 21 and 54% after LICAM(S); 91 and 87% without a ligand. In both species, about 99% of net Pu excretion (excretion with ligand - excretion without ligand) promoted in 24 hr by DTPA or LICAM(S) was in the urine, whereas about 10% of net Pu excretion promoted by the less hydrophilic LICAM(C) was in feces. Delayed excretion of both Am and Pu was significant in all ligand-treated dogs. Comparison of the nuclide content of tissues of ligand-treated mice with those of mice killed 3 min after nuclide injection indicated that the CAM ligands chelated circulating Pu and Am and prevented further deposition. In addition, the CAM ligands removed much of the presumably loosely bound Pu present in liver and skeleton at the time of ligand injection. LICAM(C) was more effective in removing Pu from liver and LICAM(S) was more effective in the skeleton. Moderate to severe uremia and histological evidence of cell killing in the distal tubules of the kidney were observed in the four dogs injected once with 30 mumole/kg of LICAM(S).(ABSTRACT TRUNCATED AT 400 WORDS)