Chromosome aberrations induced in vivo were studied in nine children 5-12 years old treated with total-body high-energy photon irradiation (pulsed exposure from a LINAC) for different types of malignant diseases. Dose-effect relationships were obtained for each child by taking blood at different times during exposure. In vitro dose-effect relationships for chromosome aberrations in children and adults were obtained by exposing blood under the same conditions as the children. Exposure in vivo and in vitro yielded similar linear-quadratic dose-effect relationships for dicentric aberrations. The response in vitro was slightly greater than in vivo, but the difference was not very large. It is concluded that the dose-effect relationship for dicentric chromosome aberrations obtained in vitro for adults can be used for biological dosimetry in irradiated children. Some of the children displayed a high number of "rogue cells" before exposure; this may be due to the malignant disease as it was not found in the healthy controls.

The study aimed to investigate whether the determination of chromosome aberrations in circulating blood lymphocytes could be useful to assess whole-body exposure from radioactive iodine released accidentally. Ten patients treated with two doses of 1850 MBq of 131 I given 24 h apart for thyroid cancer were studied for chromosome aberrations (dicentrics) in blood samples taken before and at various times after exposure. The increase in the yield of aberrations caused by the exposure to iodine was small but statistically significant. Compared to published values for whole-body doses after such treatment, this increase appears to be somewhat smaller than expected from dose-effect relationships obtained for an acute exposure of lymphocytes in vitro or in vivo, a fact which could be explained by the low dose rate of the 131 I exposure. Thus, in situations where a population was exposed as a result of the release of radioactive iodine, a determination of chromosome aberrations in blood lymphocytes would not appear to be very useful to determine exposure from iodine.

Male C57B1/Cnb and BALB/c mice were exposed to single and fractionated d(50) + Be neutrons or 137 Cs γ rays at 12 weeks of age and were followed for life-shortening and disease incidence as ascertained by autopsy and histological examinations at the time of spontaneous death. Fractionation schedules used were 10 exposures at 24-h intervals and 8 exposures at 3-h intervals for γ rays, and 8 exposures at 3-h intervals for neutrons. The data were analyzed by the Kaplan-Meier procedure using as criteria causes of death and possible causes of death. Individual groups were compared by a modified Wilcoxon test according to Hoel and Walburg (J. Natl. Cancer Inst. 49, 361-372 (1972)). No significant difference was found in C57B1/Cnb and BALB/c male mice between a single γ-ray exposure and a single neutron exposure. Gamma-ray fractionation was clearly less effective in reducing survival time than a single exposure. In contrast, fractionation of neutrons was slightly, although not significantly, more effective in reducing survival time than a single exposure. The relative biological effectiveness (RBE) for life-shortening for d(50)-Be neutrons compared to γ rays is of the order of 1 to 2 for a single exposure to neutrons and between 2 and 3 for fractionated neutrons compared to a single exposure to γ rays. Neutron irradiation caused somewhat more cancer than γ irradiation, and the RBE for cancer induction may be higher, probably between 2 and 3 in the range of 1 to 3 Gy, although the present data do not allow a more precise assessment.

C57Bl Cnb mice were exposed to single or fractionated d(50)+Be neutrons or 137 Cs γ-ray exposure at 12 weeks of age and were followed for life-shortening and disease incidence. The data were analyzed by the Kaplan-Meier procedure using as criteria cause of death and possible cause of death. Individual groups were compared by a modified Wilcoxon test according to Hoel and Walburg, and entire sets of different doses from one radiation schedule were evaluated by the procedure of Peto and by the Cox proportional hazard model. No significant difference was found in life-shortening of C57Bl mice between a single γ and neutron exposure. Gamma fractionation was clearly less effective in reducing survival time than a single exposure. On the contrary, fractionation of neutrons was slightly although not significantly more effective in reducing life span than a single exposure. Life-shortening appeared to be a linear function of dose in all groups studied. The data on causes of death show that malignant tumors, particularly leukemias including thymic lymphoma, and noncancerous late degenerative changes in lung were the principal cause of life-shortening after a high single γ exposure. Exposure delivered in 8 fractions 3 h apart was more effective in causing leukemias and all carcinomas and sarcomas than one delivered in 10 fractions 24 h apart or in a single session. Following a single neutron exposure, leukemias and all carcinomas and sarcomas appeared to increase somewhat more rapidly with dose than after γ irradiation. No significant difference in the incidence of leukemias and all carcinomas and sarcomas was noted between a single and a fractionated neutron exposure.

Two lactating cows were given tritiated hay containing organically bound tritium (OBT) only for about 4 weeks. Tritium activity was determined in milk fat, casein, lactose, milk water, and whole milk. In one cow, milk was sampled for approximately 450 days, covering two lactation periods. At steady state, specific tritium activities in casein, lactose, and milk water were 58, 10, and 11%, respectively, of those in milk fat. Some OBT was converted into THO during catabolism and entered the body water pool. This 3 H source accounted for nearly 40% of tritium in lactose, but in casein and milk fat about 97% of tritium was derived from ingested OBT. Comparison of the specific activity of milk constituents with the specific activity of ingested hay showed the following values: 0.84 for milk fat, 0.49 for casein, 0.05 for lactose, 0.10 for milk water. About one-half of the tritium transferred to milk was found in organic milk constituents and the other half in milk water. Decrease of tritium activity with time could be represented by three components with different half-lives for the organic milk constituents. Those for milk fat and casein were quite similar, with a slow component of nearly 3 months.

Cardiac β receptors in rabbits were studied at different times following lethal (5 Gy) or supralethal (10 Gy) whole-body X irradiation. Using the radioactive ligand <tex-math>$[{}^{125}{\rm I}]\text{iodocyanopindolol}$</tex-math>, it was found that the maximal binding capacity, as determined from the Scatchard plot, decreased from 298.2 ± 13.2 fmole/mg protein in controls to 142.4 ± 5.5 fmole/mg 3 days after 10 Gy whole-body X irradiation, whereas the dissociation constant was only little affected. Three days after an exposure to 5 Gy, maximal binding capacity was reduced slightly and tended toward control values at Day 7. Local irradiation of the cardiac region with 10 Gy reduced cardiac β receptors to 218 ± 7 fmole/mg (73% of control) after 3 days. The latter observation suggests that about half the effect of radiation on cardiac β receptors originates from a direct action of radiation on the heart tissue, the rest being due to abscopal systemic reactions.

Male BALB/c mice, 12 weeks old, were given a single exposure of either 137 Cs γ rays or d(50)-Be neutrons at a dose rate of 3 Gy/min. The animals were kept until death, and causes of death or possible causes of death were ascertained by autopsy and histology. The data were evaluated by competing risk methods. The survival time dose-effect curve for both types of exposure was linear and did not differ significantly (slopes: 55.8 ± 4.0 days/Gy for neutrons and 46.2 ± 4.3 days/Gy for γ rays). The incidence of different diseases also was similar for both groups except that more carcinomas, sarcomas, and myeloid leukemias seemed to occur after neutron exposure and that nonstochastic lung and kidney diseases seemed to arise at lower doses.

BALB/c male mice (12 weeks old) were exposed to a single or fractionated exposure of 137 Cs γ rays. The fractionated dose was split into 10 equal doses delivered at an interval of 1 day. The causes and possible causes of spontaneous death were ascertained by autopsy and histological examination, and the data were treated by competing risk analysis. Life shortening followed a linear dose dependency and was about the same for fractionated (38.1 ± 3.1 days/Gy) as for single (46.2 ± 4.3 days/Gy) exposure. Death from tumor disease was enhanced and that from nonstochastic lung and kidney diseases was reduced after fractionated compared to single exposure.

Pregnant sows were given tritiated water at two different doses (0.517 and 1.53 mCi/liter) during pregnancy and for 43 days thereafter (a total of 120 days). Some of the young pigs were left with their mother while the others were exchanged with uncontaminated newborn to follow tritium oxide and organic tritium in different organs with respect to (a) continuing uptake, (b) uptake from milk, and (c) loss of activity after birth. Turnover time of tritium oxide in adult sows is almost 10 days, and that in young pigs is about 8 days. In addition, components (≤5%) of slower turnover are present. At equilibrium, the relative specific activity (i.e., the ratio of specific activity of tritium oxide isolated either directly or after combustion of organic matter to the specific activity of tritiated water ingested) is about 0.7 for body water in adult and newborn pigs and about 0.14 for organic tritium in most tissues. It is somewhat higher (0.22) in the brain newborns than in other tissues. Turnover time for organic tritium in young pigs is longest in brain (59 days) and slower in muscular tissues (28 days), kidney, spleen, and pancreas (22 days), and liver and intestine (17 days). From the data presented it is estimated that the contribution of organic tritium to the integral tissue dose is on the order of one-third to two-thirds of that from tritium oxide alone, except in the case of brain, where the contribution to the dose from organic tritium may equal or even exceed that from tritium oxide.

The yields of dicentric and ring chromosomes were recorded during telecobalt therapy for mammary carcinoma. The data were fitted to a power or a quadratic function and were compared with those obtained in patients treated for ankylosing spondylitis and nuclear dockyard workers as well as with the results of an in vitro blood irradiation. As expected, the aberration yield for the same absorbed dose level is much greater after irradiation of ankylosing spondylitis than after irradiation for mammary carcinoma; lymphocytes exposed in vitro display the highest rate of aberration. A deviation of the aberrations observed in cells of the mammary carcinoma patients from the theoretical Poisson distribution also indicates that not all lymphocytes in the body had been exposed under these conditions.

Mice of the C57B1/Cnb strain were exposed to four fractionated doses delivered at weekly intervals (total doses from 4 × 50 to 4 × 375 R). One group of mice received a mixture of radioprotectors. The animals were followed to their natural death and investigated for histopathology. Life-shortening showed a sigmoid dependency on the dose in nonprotected and protected mice with a dose reduction factor of 2.1 at 50% life-shortening. Thymic lymphoma was the most predominant cause of death in irradiated C57B1 mice. Radioprotectors diminished significantly the incidence of this disease but apparently did not reduce other causes of death. Reticulum cell sarcoma B also increased at the same low doses as thymic lymphoma. Both thymic lymphoma and reticulum cell sarcoma B increased in frequency after a fractionated dose compared to a single exposure with doses of 600-700 R and 300-400 R, respectively.

The responses of blood pressure and mesenteric blood flow were recorded during infusion of biogenic amines (noradrenaline, dopamine, serotonin, acetylcholine, and histamine) to control and X-irradiated rats (first and third days after 2 kR X irradiation). Responses to different doses of the amines were evaluated, and the results obtained correspond to those seen in other species (e.g., an increase in pressure and a decrease in flow with an overshoot after infusion of noradrenaline, an increase in pressure and flow after dopamine, an increase in pressure and a decrease in flow after serotonin, a decrease in pressure and flow after acetylcholine, and a decrease in pressure and an increase in flow after histamine). Irradiated animals are more responsive to pressure-raising agents, in particular to noradrenaline. They also have an altered dose-pressure response curve for dopamine.

Male BALB/c or C57Bl mice were exposed to different doses of X rays. Certain groups were given a mixture of protectors or AET prior to irradiation; others served as controls. The animals were followed until spontaneous death, and the lethal diseases were classified as thymic lymphoma, nonthymic lymphoma, reticulosarcoma, myeloid leukemia, lung carcinoma, liver tumors, sarcoma, glomerulosclerosis, noncancerous lung lesions, and others. The data were evaluated by the method of competing risks. Death in nonirradiated BALB/c mice is largely caused by tumors, in particular by lung cancer and nonthymic lymphoma, whereas other causes predominate in the C57Bl strain. Radiation-induced life shortening of nonprotected mice is due to increased and advanced incidences of specific diseases, mainly thymic lymphoma in the medium dose range and glomerulosclerosis in the high dose range. Thymic lymphoma in BALB/c mice increases to a maximum at 650 R and declines thereafter. A shorter latency period is found for lung carcinoma, although the absolute incidence decreases because of the earlier deaths of the irradiated mice. After AET treatment the maximum incidence of thymic lymphoma in BALB/c mice is shifted to 1000 R but its height is unaltered, whereas treatment with a mixture not only displaces the maximum to a still higher dose but also decreases its frequency. Protection in BALB/c mice is also possible, although to a smaller extent, against myeloid leukemia, sarcoma, glomerulosclerosis, and noncancerous lung lesions but it is protection against the two latter diseases which contributes most to the prolonged survival in the high dose range. The protection in C57Bl mice resembles that in the BALB/c strain. Thus protection is effective against thymic lymphoma (possibly also against liver adenomas, all carcinomas, and myeloid leukemia) as well as against glomerulosclerosis and noncancerous lung lesions.

The right hemithorax of rats was exposed to 3 kR of X rays; the animals were sacrificed at different times after exposure up to 9 months, and various biochemical parameters were determined. After a slight early decrease, collagen increased during the fibrotic stage. An increase during fibrosis was also seen for DNA, β-glucuronidase, cathepsin, histamine, serotonin, and lipid peroxides. Fibrinolytic activity was found to be depressed at most time points studied.

Death from the gastrointestinal syndrome after whole body irradiation is usually thought to result from the loss of electrolytes into the intestine subsequent to the depletion of cells from the villi. The data presented cast doubt on the primary role of electrolyte loss in the G. I. syndrome in rodents. The loss of Na + in feces and intestinal tract is less than 10% of the body pool and occurs over the whole postirradiation period. Na + diminishes in blood however only during the few hours immediately prior to death concomitantly with a decrease in plasma volume. Replacement therapy with Na + (as well as antibiotica, plasmaexpander glucose) does not increase survivial time although under these conditions sufficiently Na + is kept in the body to cause considerable renal excretion. Na + absorption after irradiation is diminished when little Na + is present in the lumen but it can even exceed normal Na + absorption at high concentrations in the lumen. This behavior is explained by the fact that after irradiation active Na + absorption is abolished. No excessive loss of Na + into the lumen is observed in perfused intestinal preparations. It is postulated that not electrolyte loss into the intestine but rather changes in permeability in all organs leading to a state of irreversible shock is responsible for death.

Regeneration of thymus, spleen and bone marrow of AKR/T1 Ald mice after whole body irradiation with 605 rad (650R) with or without treatment with 10 7 syngeneic bone marrow cells from AKR mice was followed. In the non-transplanted irradiated animals, cell division recommences first in the thymus (on day 6) following the biphasic pattern observed by others. Cell division in spleen (day 8) and bone marrow (day 8-12) resume later. After bone marrow treatment, all these organs begin to regenerate at about day 6 and also display a biphasic pattern of cell divisions. The proportion of donor cells remains high in bone marrow and spleen, but drops temporarily in thymus, perhaps as the result of division of damaged thymus cells. The data interpreted in a semiquantitative way suggest that the assumption that the thymus is seeded from bone marrow, is not needed to explain a biphasic pattern of thymus regeneration, rather it appears likely that cells present in thymus or deposited there immediately after injection of bone marrow cells can engender a full regeneration of the thymus.

Uptake and catabolism of 131 I-labeled denatured albumin was studied in perfused liver isolated from fed, starved, and starved x-irradiated (24 hours after 800 R) rats. Uptake of albumin and proteolytic activity is greater in starved rats than in fed rats. X-Irradiation depresses the uptake of albumin by the liver but does not affect or even increases proteolytic activity.

<tex-math>$\text{Deoxycytidine-}2\text{-}{\rm C}^{14}$</tex-math> was injected into rats or mice and the animals were subjected to total body irradiation 1 day later. DNA in organs and metabolites in urine were isolated and their activity determined. Radioactivity in lymphoid organs decreased, whereas the total and specific radioactivity of the deoxycytidine excreted increased on the first day after exposure. This observation indicates that deoxycytidine excreted after irradiation originates from degraded DNA, since the specific activity should decrease if precursors not utilized for DNA syntheses were the main contributors to deoxycytidinuria. Experiments in which <tex-math>${\rm C}^{14}\text{-deoxycytidine}$</tex-math> was given after exposure confirmed this assumption.

Catabolism of a mixture of 3 H-labeled serum proteins was studied in the perfused liver of normal rats and of rats 3 to 5 days after total-body irradiation (850 R). A significant decrease in radioactivity during the 12-hour perfusion period was observed only for prealbumin and $\alpha _{2}\text{-globulins}$ . Catabolism of serum proteins in the liver appeared to be unchanged after irradiation. Catabolism of a mixture of ${}^{131}{\rm I}\text{-}$ and ${}^{3}{\rm H}\text{-phenylalanine-labeled}$ serum proteins was studied in intact normal rats and in rats injected immediately after total-body exposure (800 R). The activity of total protein as well as that of prealbumin, albumin, α 1 -, α 2 -, and γ-globulins decreased on the fourth day after irradiation below control levels. Thereafter the activity-time curves for most protein fractions of X-irradiated rats paralleled those of the control rats, except that the activity in albumin and γ-globulin decreased in the X-irradiated rats at a much faster rate. It is suggested that serum proteins are lost more rapidly from the circulation, owing to changes in the distribution between the extra- and intravascular space or to a more pronounced extrahepatic catabolism.