Fission fragment RBE for bone sarcoma induction.

Thirty beagles and 277 mice were injected with 249Cf, and 30 beagles and 274 mice were injected with 252Cf. The skeletal dose (in Gy) from 252Cf was about half from fission fragments and half from alpha particles, whereas 249Cf emits alpha particles in 100% of its transformations. Bone sarcomas (mostly osteosarcomas) were the main radiation-induced cancer. The relative biological effectiveness (RBE) of fission fragment dose relative to alpha-particle dose for bone sarcoma induction was calculated from the ratio of 249Cf/252Cf doses at equal times to bone sarcoma in (a) beagles and (b) mice, and (c) from the ratio 252Cf/249Cf risk coefficients in mice. The average RBE +/- standard deviation of the three evaluations was 0.1 +/- 0.1. The very low RBE for bone sarcomas is supported by the data of A. L. Batchelor, T. J. Jenner, and L. M. Cobb [Phys. Med. Biol. 28, 475-483 (1983)] for lung cancer induction in rats and by that of A. L. Brooks, J. A. Mewhinney, and R. O. McClellan [Health Phys. 22, 701-706 (1972)] for producing chromosome aberrations in the liver cells of Chinese hamsters. The low effectiveness of fission fragments relative to alpha particles, per gray of absorbed dose, is ascribed primarily to the much larger number of cells traversed by the alpha particles. Consideration might be given to decreasing the quality factor of fission fragments by an order of magnitude below that for alpha particles.

Retention and dosimetry of injected 241Am in beagles.

Equations have been derived, from the results of total-body and partial-body counting and gamma-ray counting of individual bones and soft tissues, which describe the retention of injected 241Am in the liver, in the nonliver tissue (including skeleton), and in the skeleton of young adult beagles. Retention was found to be dependent upon injection level, and different sets of equations were developed for dogs given about (a) 2.8 microCi/kg (b) 0.9 microCi/kg (c) 0.3 microCi/kg, and (d) 0.1 microCi/kg and less. Liver rention, RL, was characterized by a single exponential equation of the form RL = ce-beta t, with c = 0.49 +/- 0.04 and beta = a function of injection level. Nonliver tissue was assigned a retention equation of the form RNL = d + alpha + J(l - e-mt), with d = 0.102 +/- 0.024 e-1.22t, alpha = 0.41 +/- 0.04, and both J and m as a function of injection level. Skeletal retention was found to be about 0.885 +/- 0.037 of nonliver retention with no significant dependence upon either injection level or time after 241Am injection. Dosimetry equations based on these retention expressions were derived. Individual bones of 55 beagles were assayed at death for their 241Am content for a determination of 241Am distribution within the skeleton.

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)

228Th retention and dosimetry in beagles.

Total-body and skeletal retention of 228Th were determined in a group of 104 young adult male and female beagles for about the first 7 years after the injection of 0.00159 to 2.76 muCi/kg. Ratios of 224Ra / 228Th , 212Pb / 228Th , and 212Bi / 228Th in the skeleton and in soft tissues of 20 beagles were measured as a function of time after injection. A humerus, femur, and ulna from 20 dogs dying 7 to 554 days after injection were sectioned, and the 228Th concentration was obtained for each piece. Percentage biological retention in the skeleton of 228Th at t days after injection could be described as 68.1 e-0. 000180t . Ratios of daughter-to-parent activity in soft tissue showed no definite trend with dose level or time and averaged Ra/Th = 0.56, Pb/Th = 0.83, and Bi/Th = 0.91, whereas the ratios for the skeleton varied with both dose level and time. Ratios of activity in the skeleton from lowest to highest dose level after 2 years following injection ranged between Ra/Th = 0.88 to 0.95, Pb/Th = 0.78 to 0.92, and Bi/Th = 0.77 to 0.90. Retained 228Th was deposited most heavily in parts of the skeleton with much trabecular bone, much bone surface area, and high bone remodeling rates. No changes in this deposition pattern could be discerned during the 554 days over which the measurements of sectioned long bones were made.

Radiation dose rates to the proximal humerus of growing beagles injected with 239Pu.

The anatomical distribution of 239Pu in the proximal humerus was studied in four beagles injected at 90 days of age and sacrificed 7, 28, 56, and 128 days after injection, respectively. Initial deposition in each humerus was 3.1% of the injected Pu; 41% of that was retained with a net halftime of 248 days; for the remaining 59% no decrease was observed with time. Sixty-one percent of the initial deposit was concentrated in the proximal epiphysis and metaphysis. Average radiation dose rates to trabecular bone of the epiphysis, to those parts of the metaphysis that were formed before and/or after injection, and to the area corresponding to the primary and secondary spongiosa were determined by fission track autoradiography. Local dose rates within the range of 10 microns of the endosteal surface, to the marrow and to osseous tissue were calculated. Because of the rapid growth and modeling rate, surface deposits declined rapidly. In the metaphysis, bone formed after injection contained less than 1/2 the Pu concentration of bone which was present at the time of injection. At 100 days of age, bone mineralization as determined by the ash weight/wet weight ratio, and the fraction of bone volume occupied by mineralized tissue was 1/2 that seen in young adult beagles. The surface/volume ratio was twice as high as in young adult beagles. The possible effects of local radiation doses were correlated with areal densities of cells and types of cells at risk. Comparisons were made with corresponding sites from the humerus of beagles injected as young adults.

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.

Radium retention and dosimetry in juvenile beagles.

Retention of administered 226Ra was substantially greater in beagles injected as 3-month-old juveniles than as 1.4-year-old young adults, but the measured 222Rn/226Ra ratio in bone was significantly less in juveniles for about the first 600 days after injection. An equation that describes the total-body biological retention R in beagles injected with 226Ra at 3 months of age at any time t (in days) after injection during the first 6.6 years is R = 0.331e-0.206t + 0.245e-0.00374t + 0.424e-0.000114t. The rate constant of the final term in the equation for juveniles is similar to that for young adults, suggesting that this component reflects the net turnover rate in the slowly remodeling component of adult bone. Compared to young adult beagles, animals injected as juveniles had a greater fraction of their retained 226Ra in parts of the skeleton containing much cortical bone, such as paws, and a smaller fraction in those parts containing much trabecular bone.

Skeletal retention and distribution of 226Ra and 239Pu in beagles injected at ages ranging from 2 days to 5 years.

The age at exposure significantly affects the retention and distribution of 226Ra and 239Pu, both of which deposit in the skeleton although in somewhat different patterns. Beagles aged 2 days (neonates), 90 days (juveniles), 18 months (young adults), or 5 yrs (mature) received a single subacute injection of one of these nuclides and were sacrificed serially during a 2-yr interval. Nuclide concentrations in plasma, the skeleton, individual bones and bone sections were determined and retention equations were calculated. The microanatomical skeletal nuclide distribution was studied after fission track or conventional autoradiography. Elimination of 239Pu and its translocation from bone surfaces to the bone volume caused by bone growth and turnover processes were measured. Average radiation doses and dose rates as a function of age at exposure were determined. Initial uptake and retention, skeletal nuclide concentration, proliferative activity of local cell populations and residence time of the nuclide on skeletal surfaces were affected significantly by age at exposure. The effect of these parameters on tumor induction is discussed. This study has provided early retention and distribution data which together with data from a chronic toxicity study will be used to estimate the risk of Pu exposure relative to that of Ra to humans of all ages.