Effects of the single or repeated inhalation exposure of Syrian hamsters to aerosols of 239PuO2

Male Syrian hamsters were scheduled to be exposed by inhalation approximately every 60 days for 1 year (7 exposures) to aerosols of 239PuO2 beginning at 84 days of age. Other hamsters were exposed once when 84 or 320 days of age. Plutonium-239 deposited in the lungs by the repeated inhalation exposures was cleared from the lungs at a rate similar to that following a single inhalation exposure. The incidence of radiation pneumonitis, bronchiolar epithelial hyperplasia, and alveolar squamous metaplasia were the only lesions that were related to radiation dose. Only two primary lung tumours were found among the hamsters exposed to 239PuO2. No primary lung tumours were found in the control hamsters. It was concluded that the incidence of lung tumours was not increased by the protraction of the alpha radiation dose to the lungs from repeated inhalation exposure.     

Repeated inhalation exposure of rats to aerosols of 144CeO2. I. Lung, liver, and skeletal dosimetry.

To develop a better understanding of the influence of cumulative radiation dose and dose rate to the lungs on the biological responses to inhaled radionuclides, several studies are in progress at this institute in which laboratory animals have been exposed once or repeatedly to aerosols of insoluble particles containing 144Ce or 239Pu. In the study reported here, F344 rats were exposed repeatedly to aerosols of 144CeO2 beginning at 94 days of age to reestablish desired lung burdens of 1.9, 9.2, 46, or 230 kBq of 144Ce every 60 days for 1 year (seven exposures). Other 94-day-old rats were exposed once to achieve similar desired initial lung burdens of 144Ce. Older rats were exposed once to achieve desired initial lung burdens of 46 or 230 kBq when 500 days of age, the age of the repeatedly exposed rats when exposed for the last time. Control rats were either unexposed, sham-exposed once or repeatedly, or exposed once or repeatedly to stable CeO2. Approximately equal numbers of male and female rats were used. The cumulative beta-radiation doses to the lungs, liver, and skeleton of rats exposed repeatedly were similar to those of rats with similar total lung burdens of 144Ce from a single inhalation exposure. The average beta-radiation dose rate to the lungs of the rats exposed repeatedly was about one-fifth of that in rats with similar total lung burdens after a single exposure.     

Influence of dose rate on survival time for 239PuO2-induced radiation pneumonitis or pulmonary fibrosis in dogs.

Beagle dogs were exposed once or repeatedly to 0.75-microns-diameter monodisperse aerosols of 239PuO2 by pernasal inhalation. The dogs that were exposed once received alveolar depositions (+/- standard deviation) of 3.9 +/- 1.9 kBq/kg body mass and accumulated doses of 23 +/- 8 Gy to the lung before death at 5.4 +/- 1.7 years after exposure. Dogs exposed repeatedly received a total alveolar deposition of 5.3 +/- 0.9 kBq/kg body mass during 7 to 10 semiannual exposures and accumulated doses of 22 +/- 5 Gy to the lung before death at 4.9 +/- 0.7 years after first exposure. Clearance of the plutonium from the lung in the dogs exposed repeatedly was slower than in the dogs exposed once. All dogs in the repeated-exposure study and all but one dog in the single-exposure study died from radiation effects. Pulmonary fibrosis accounted for 72% of the radiation-related deaths in the single-exposure study and 87% in the repeated-exposure study. The remaining dogs died with pulmonary cancer. Based on total cumulative radiation dose, the times after exposure to death from radiation pneumonitis and pulmonary fibrosis were not significantly different for single and repeated exposures. Thus dose rate does not appear to be an important factor in predicting death from radiation pneumonitis or pulmonary fibrosis for dogs inhaling 239PuO2.     

Cardiopulmonary function of dogs with plutonium-induced chronic lung injury

Beagle dogs had signs of restrictive lung disease 1 to 5 years after exposure by inhalation to 239PuO2 aerosols. The 239PuO2 aerosols were monodisperse with activity median aerodynamic diameters of 0.75, 1.5, or 3.0 microns. The plutonium particles produced protracted alpha irradiation of the lungs. Ten dogs had specific initial pulmonary burdens (IPB) of 330 to 4,100 kBq of 239PuO2/kg of body mass. The average onset time of clinical signs of lung injury was 3 years after exposure; the average time from the onset of signs until cardiorespiratory function evaluation was 5.5 years. A second group of 10 dogs had IPB of 110 to 2000 kBq of 239Pu/kg of body mass but no signs of lung injury. A third group of 10 dogs, not exposed to 239Pu, were matched for age and sex. Cardiopulmonary function tests were performed. Only the dogs in group I with signs of lung injury had a mild respiratory function disorder consisting of smaller lung volumes, reduced compliance, increased respiratory frequency and minute volume, and reduced carbon monoxide diffusing capacity. Cardiac function of all three groups was similar. These findings indicate that alpha irradiation of the lungs of man could produce restrictive lung disease at long times after initial exposure.     

Repeated inhalation exposure of rats to aerosols of 144CeO2. II. Effects on survival and lung, liver, and skeletal neoplasms.

Groups of 94-day-old F344/Crl rats were exposed repeatedly to aerosols of 144CeO2 to reestablish desired lung burdens of 1.9, 9.2, 46, or 230 kBq of 144Ce every 60 days for 1 year (seven exposures). Other 94-day-old rats were exposed once to achieve similar desired initial lung burdens of 144Ce. Older rats were exposed once to achieve desired initial lung burdens of 46 or 230 kBq when 500 days of age, the same age at which rats had the last of the repeated exposures. Control rats were either unexposed, sham-exposed once or repeatedly, or exposed once or repeatedly to stable CeO2. Approximately equal numbers of male and female rats were used. The median survival time and cumulative percentage survival curves were significantly decreased only in male and female rats exposed repeatedly to reestablish a 230-kBq lung burden and among the 94-day-old male rats exposed once to achieve a 230-kBq lung burden of 144Ce. The crude incidences of primary lung cancers (well described by a single Weibull distribution function), time to death with lung tumors, and risk of lung cancer per unit of beta-radiation dose to the lungs were correlated with the cumulative beta-radiation dose rather than the rate at which the dose was accumulated. A linear function, 70 (+/- 7.3) + -0.15 (+/- 0.056) x dose (+/- SD), adequately described the excess numbers of rats with lung cancers over a beta-radiation dose range to the lungs of 6.8 to 250 Gy for two groups of rats with the highest doses to the lungs after a single exposure and for two groups with the highest doses after repeated exposure.     

The development and interlobar distribution of plutonium-induced pulmonary fibrosis in mice

Six-week-old mice were exposed by inhalation to an aerosol of 239PuO2 (activity median aerodynamic diameter 2.2 microns) to establish mean alveolar depositions at 2 days after exposure of 4, 40, and 930 Bq of 239Pu. Animals were killed serially after 3, 6, 12, and 18 months at which times the development of the pulmonary fibrotic lesion was assessed by both biochemical and histopathological techniques. Individual measurements of both fresh and dry weights, protein, DNA, and hydroxyproline were made on whole lung and also on each of the five constituent lobes. Early and sustained increases in lung mass, lung protein, and total lung collagen were found, together with a depression of the total cellularity of the lung at 6 and 12 months after exposure. Although at later times compensatory hypertrophy of less affected areas distorted the relationship, systematic trends in the severity of responses between lobes were found. These trends were related to the initial lobar concentrations of 239Pu.     

The induction of liver tumors by 239Pu citrate or 239PuO2 particles in the Chinese hamster

The influence of radiation dose distribution on the frequency of 239Pu-induced liver tumors was evaluated in the Chinese hamster. Different concentrations of 239Pu citrate 239PuO2 particles of known sizes were injected intravenously via the jugular vein. About 60% of the injected 239Pu citrate was deposited in the liver and 40% in the bone. The 239Pu citrate was rather uniformly distributed throughout the liver parenchyma. Injected plutonium oxide particles were taken up by the reticuloendothelial system with 90% of the body burden deposited in the liver. The 239PuO2 particles were localized in the Kupffer cells and produced nonuniform dose distributions that were dependent on particle size. There was an activity- and dose-dependent increase in the incidence of total liver parenchymal cell tumors following injection with either plutonium particles or citrate. For animals that received 14.0-, 2.7-, 0.3-, and 0.04-Gy dose to liver from 239Pu citrate the cumulative tumor incidence was 39, 32, 5, and 0%, respectively. Animals that were injected with the 0.24 micron 239PuO2 particles had doses of 42.0, 7.2, and 0.8 Gy to the liver and tumor incidences of 34, 26, and 5%, respectively. Plutonium citrate also produced hemangiosarcomas of the liver and tumors in bone and bone marrow. The latent period for liver tumor appearance in animals exposed to 239Pu citrate or 239PuO2 particles increased as the injected activity decreased. For animals injected with a similar total activity (7.4 Bq/g), the lifetime cumulative liver tumor incidence was similar for animals exposed to either 239Pu citrate (32%) or 239PuO2 (26%). There was little effect of particle size on liver tumor incidence. These data indicate that, in Chinese hamster liver, local radiation dose distribution is less important in altering tumor incidence than injected activity or average dose. However, the more uniform irradiation from 239Pu citrate administration was more effective in cancer production than the nonuniform irradiation from 239PuO2 particles.     

Pathogenetic process of lung tumors induced by inhalation exposures of rats to plutonium dioxide aerosols

Sequential examinations were done on the pulmonary cytokinetics and pulmonary lesions in rats after inhalation exposure to (239)PuO(2) aerosols to investigate the pathogenesis of lung tumors. Total cell yields of lavaged bronchoalveolar cells as well as the estimated numbers of pulmonary alveolar macrophages were significantly reduced from 1 to 3 months after exposure but recovered thereafter to the control levels. The proportions of multinucleated or micronucleated pulmonary alveolar macrophages increased significantly in lavaged cells from 1 month, and the increase was sustained up to 18 months after exposure. Both tumor necrosis factor and nitric oxide were shown to be differentially released from stimulated cultures of pulmonary alveolar macrophages during the period from 6 to 18 months after exposure. The labeling indices of alveolar and bronchiolar epithelial cells treated with 5-bromo-2'-deoxyuridine increased significantly in lungs from 3 months and were sustained up to 18 months after exposure. Histopathological examinations revealed that after the early inflammation, hyperplasia and metaplasia of the lining of the bronchioloalveolar epithelium were predominant from 3 to 6 months, while adenomatous or adenocarcinomatous lesions appeared and developed from 12 months after exposure. The appearance of primary lung tumors, almost all of which were adenomas and adenocarcinomas, was found in the dose range of 1 to 2 Gy from 12 months after exposures. These results indicate that the pathogenetic process initiated by early cellular damage and alterations associated with inflammation is followed by the proliferative and metaplastic lesions of pulmonary epithelium, leading to the appearance and development of pulmonary neoplasms from 1 year after the inhalation exposures in rats that received a minimum lung dose of more than 1 Gy.     

Promotion of pulmonary carcinogenesis by plutonium particle aggregation following inhalation of 239PuO2

Promotion of lung tumor formation from inhaled 239PuO2 in rats may be associated with aggregation of plutonium particles near bronchioles. The relationship of plutonium particle aggregation in the lung and the development of lung tumors after inhalation of 239PuO2 was studied in 664 life span rats with mean lung doses ranging from 0.35 to 20 Gy. Plutonium particle concentration and aggregation were determined from autoradiographic sections of the left lung lobe. The increase in particles/cm2 and mean number of particles per aggregate up to 20 Gy were directly proportional to lung dose. Aggregates with greater than 25 particles increased linearly with dose from 0.2% at 1.4 Gy to 8.2% at 20 Gy, in a pattern similar to increasing severity of pulmonary fibrosis and incidence of lung tumors. Lung tumor incidence increased from about 6% at 1.4 Gy to 83% at 8 Gy; no further increase in lung tumors was seen at doses greater than 8 Gy. Maximum lung tumor incidence at 8 Gy corresponded to a particle concentration of 130/cm2 and four particles/aggregate with 4% of aggregates having greater than 25 particles. Aggregation of inhaled plutonium particles in clusters of greater than 25 particles resulted in daily doses of only a few centigray to focal tissue regions containing clustered particles, yet these doses appeared sufficient to cause pulmonary fibrosis and promotion of pulmonary carcinogenesis.     

Macrophage depletion of mouse lung following inhalation of 239PuO2

Changes in the free-cell population of the lungs of two strains of mice (SAS/4 and CBA/H) were studied up to 4 months after inhalation exposure to a sized fraction of 239PuO2 particles (1.5 micron AMAD) to give initial alveolar depositions (IADs) ranging from 17 to 810 Bq. A sample of the free-cell population of the lung was recovered by bronchoalveolar lavage, and a radiometric method was used to estimate the total number of pulmonary alveolar macrophages (PAM) in the lung. The response of the lung to 239PuO2 was characterized by an initial, dose-dependent depression in the total number of PAM following an IAD as low as 50 Bq. At IADs greater than 150 Bq, the initial depression continued for longer, merging into a chronic phase in which the PAM were larger and were accompanied by a minor infiltration of leukocytes. These findings were confirmed by histology, which also revealed focal accumulations of Type II pneumocytes. The results indicate that inhaled alpha-emitting particles are effective at producing a depletion in the alveolar macrophage population at relatively low IADs and that chronic effects on the cells can be produced by higher concentrations.     

Influence of radiation dose patterns on lung tumor incidence in dogs that inhaled beta emitters: a preliminary report

Different radiation dose patterns to the lung from inhaled beta-emitting radionuclides may influence the frequency and kind of biological effects. To determine the magnitude of this influence, groups of Beagle dogs were exposed to aerosols of 90Y, 91Y, 144Ce, or 90Sr in relatively insoluble particles and observed for their life spans. Different dose patterns were achieved by using these radionuclides having similar beta emissions and chemical form but having physical half-lives ranging from 2.6 days to 28 years. The range of initial lung burdens of radionuclides studied resulted in a range of biological effects from early deaths at the highest radiation doses to no discernible effects at the lowest doses. The effective half-lives of the four radionuclides in the lung ranged from 2.5 to 600 days. Within 1.5 years after exposure, some dogs died with radiation pneumonitis and pulmonary fibrosis. Between 1.5 and 10 years after exposure, 42 pulmonary carcinomas and 28 pulmonary sarcomas were observed in 163 dogs that died. Protracted irradiation of the lung from 90Sr or 144Ce resulted in a relatively high radiation dose and produced more total lung tumors but fewer lung tumors per rad than less protracted irradiation from 90Y or 91Y. At 10 years after inhalation exposure, the difference in risk per rad among the different dose patterns was a factor of 4 to 8, indicating that the different radiation dose patterns from inhaled beta emitters do influence lung tumor risk factors, at least at high (greater than 20,000 rad) doses to lung.     

Preliminary studies of the interaction between 239PuO2 and cigarette smoke in the mouse lung

Our current experiments were designed to show whether 12 months' exposure to cigarette smoke enhances the incidence of lung tumours in mice that had previously inhaled 239PuO2. These periods of smoke exposure are almost complete. After death their lungs will be cleared and any nodules found will be sectioned for histopathology. This paper reports the results of two preliminary experiments conducted earlier. The first study showed that mice could tolerate the proposed smoking regime for 3 months, with no sign of ill health in any animal throughout. The major difference found was a reduced growth rate in both smoke- and sham-exposed mice relative to that of cage controls. After 3 months of treatment, histopathology and morphometry of lung sections found only slight smoke-induced changes. These included a reduced proportion of alveolar space and an increased number of pulmonary alveolar macrophages (PAM) per unit area. Bronchopulmonary lavage showed that the PAM from smoke-exposed mice were larger than those from sham-exposed or control mice and that an increased proportion of cells were binucleate. All mice in the second study were initially exposed to 239PuO2, then subsequently divided into three treatment groups as above. Cigarette smoke exposure was shown to inhibit the removal of 239Pu from the lung whilst sham exposure had no effect. Smoke exposure also produced an increase and sham exposure a decrease in lung weights relative to those of cage controls. The latter was probably as a result of their lower growth rate. In our current experiments it is likely that the group receiving 239PuO2, then smoke, will receive a higher radiation dose to lung than those receiving 239PuO2 only. Any increased tumour incidence found will be considered in conjunction with this evidence.     

Single inhalation exposure to 90SrCl2 in the beagle dog: hematological effects

The toxicity of 90Sr administered by the inhalation route was studied in young adult Beagle dogs exposed once to aerosols containing 90SrCl2. Due to its relatively soluble chemical form, 90Sr was rapidly translocated from lung to bone where a substantial portion was retained for a long period of time. This resulted in only a brief radiation exposure of the respiratory tract and a protracted exposure of the skeleton. The long-term retained burdens ranged from 0.037 to 4.4 MBq 90Sr/kg body wt. Dogs were subsequently observed throughout their life span. Six dogs with long-term retained burdens of 1.7 to 4.1 MBq 90Sr/kg died at less than 32 days after exposure from radiation-induced bone marrow hypoplasia. Review of hematological parameters of all dogs showed a similar, consistent, and dose-related pancytopenia in those animals having a long-term retained burden of greater than 0.37 MBq 90Sr/kg. Thrombocytopenia and neutropenia persisted in all exposed dogs through 1000 days after exposure. For reference purposes, a burden of 0.37 MBq 90Sr/kg is calculated to deliver an average radiation dose to the skeleton over 30, 100, and 1000 days after intake of 1.0, 2.8, and 17 Gy, respectively. The hematologic changes were similar to those seen in people exposed to high doses of whole-body external radiation.     

Microdosimetry of rat alveolar type II cells irradiated with alpha particles from 239PuO2

The alveolar type II cell is one of the critical cells for radiation damage in the lungs after inhalation of radioactive aerosols. With the aid of a Quantimet-970 image analyzer and a VAX-11/780 computer, we calculated the radiation dose to rat alveolar type II cells from alpha particles emitted by 239PuO2. A series of dosimetric parameters for type II cells, including track length distribution, linear energy transfer (LET), values of the specific energy for a single hit of a spherical target (z1), cellular dose, hit number, and their spatial distributions were calculated. By comparing the volume density of type II cells and lung tissue with energy deposited in alveolar type II cells, we found that the energy deposited per unit volume of type II cells was larger than that of lung tissue excluding type II cells. The z1 for spherical targets and the LET across type II cells were less than those in lung tissue excluding type II cells. The age of the rat and damage to lung by inhalation may significantly influence some of the parameters. The neoplastic transformation probability for type II cells is also discussed. The results suggest that the type II cell is an important target cell in the rat lung for exposure to inhaled 239PuO2.     

Distribution and biological effects of inhaled 239Pu(NO3)4 in cynomolgus monkeys.

Twenty male cynomolgus monkeys were exposed by inhalation either to an aerosol of 239Pu(NO3)4 to produce projected initial lung burdens of either 40, 10, or 4 kBq or to a carrier aerosol as a control. Animals died or were sacrificed at 0.01, 1, 3, 6, 12, 24, 40, and 99 months after inhalation, and the distribution and biological effects of the 239Pu were determined. The 239Pu cleared efficiently from the lungs so that less than 0.05 kBq remained at 99 months after exposure to 40 kBq. Total skeletal 239Pu activity was nearly constant after the first year, but the fraction of the body burden in skeleton at sacrifice increased with time up to 99 months because of clearance from other organs. Plutonium in the liver increased to a peak at 1 year and then decreased to about 10% of the peak value at 99 months. Plutonium in the testes was localized in the interstitial tissue with only 0.01 to 0.002% of the projected lung burden remaining in testes at 99 months after inhalation. Three animals exposed to 40 kBq of 239Pu died of radiation-related pulmonary pneumonitis and fibrosis. A primary papillary adenocarcinoma of the lung was identified in one animal exposed to 40 kBq initial lung burden and sacrificed 99 months after inhalation. The frequency of chromosome aberrations in blood lymphocytes was significantly elevated only in monkeys with projected deposits of 40 kBq of 239Pu. There was no change in aberration frequency in other exposure groups as a function of inhaled activity, time after exposure, or calculated total dose to the lungs. Only in monkeys that had marked radiation-induced pathological changes in the lung did the frequency of chromosome-type aberrations increase significantly, to a value about twice the control level. In cynomolgus monkeys, chromosome aberration frequency in blood lymphocytes is not a good indicator of radiation dose or damage from inhaled soluble plutonium.     

Strain differences in carcinogenic and hematopoietic responses of mice after injection of plutonium citrate

The carcinogenicity of injected (239)Pu citrate was compared in female mice of the C3H, C57BL/6 and BC3F(1) hybrid strains with different spectra of spontaneous or radiation-induced tumors. A significant reduction in survival due to early death caused particularly by the induction of osteosarcomas was noted in each strain after injection of 500 Bq or more. The dose response of osteosarcomas appeared to have a similar pattern in each strain except for the differences in the skeletal dose ranges for the maximum induction. While the incidence of lymphoid tumors decreased as that of osteosarcomas increased sharply to the maximum at higher doses, their histological phenotypes were predominantly non-thymic, pre-B-cell leukemic lymphomas compared to the controls in each strain. Myeloid leukemias were not highly induced in any of the control and (239)Pu-injected mice, and solid tumors involving the other organs were reduced in each strain after injection of 500 Bq or more. To follow up the hematological kinetics related to alpha-particle irradiation of bone marrow stem cells, sequential examinations were done in mice of each strain within 1 year after injection of 5000 Bq. The numbers of peripheral white blood cells and bone marrow cells were consistently reduced in each strain from 90 days on, while spleen cells increased from 180 days on. Granulocyte-macrophage and macrophage colony-forming cells were also consistently reduced in the bone marrow, with a compensatory increase in the spleen from 90 days on. These findings indicate that the carcinogenic and hematopoietic responses were specific to alpha-particle irradiation and were independent of mouse strain after injection with (239)Pu citrate.     

Relative toxicity of chronic irradiation by 45Ca beta particles and 242Cm alpha particles with respect to the production of lung tumors in CBA/Ca mice

Approximately 1800 female CBA/Ca mice were exposed by inhalation at three dose levels to beta particles from (45)Ca-labeled fused aluminosilicate particles (FAP), to alpha particles from (242)Cm-labeled FAP, or to carrier control FAP. Another group of mice inhaled no FAP and were designated as untreated cage controls. The FAP in combination with these radionuclides was used to achieve the same spatial and temporal distribution of alpha- and beta-particle dose within the irradiated mice. Some mice were killed to determine the clearance of radiolabeled FAP from their lungs, and the remainder were allocated to a life-span study. All animals were subjected to a detailed necropsy. To facilitate the identification of small tumors, the lungs were rendered transparent in methyl salicylate and examined under back illumination for the presence of lesions. Lung nodules and other microscopic lesions were excised for histological examination. The median survival of mice in all groups was approximately 910 days. The control animals lived longer than those that were irradiated, but it was difficult to determine a dose-response relationship for survival among the exposed mice. Benign adenomas and, less frequently, malignant adenocarcinomas were identified in all animal groups. The prevalence of these tumors was approximately 28.8% in the control mice, which is consistent with the results of other studies using the same strain of mouse. After exposure to radionuclide-labeled FAP, there was a significant dose-related increase in the prevalence of lung tumors in (242)Cm- (peak prevalence 55%) and (45)Ca-exposed (peak prevalence 48.6%) mice. The prevalence of tumors in the mice that received (242)Cm-labeled FAP was approximately twice that in the mice that inhaled (45)Ca-labeled FAP within the range of doses employed (0.55-4.69 Gy). Using the ratio of the slope of the linear component of the dose-response curves, the toxicity of the alpha particles relative to the beta particles was 1.5 (90% CI: 0.7, 9.0) for all adenomas and 9.4 (90% CI: 5.0, 23.0) for the less frequent adenocarcinomas. The relative toxicity for adenocarcinomas was found to decrease with increasing dose.     

Activation of alveolar macrophages after plutonium oxide inhalation in rats: involvement in the early inflammatory response

Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO2 of different isotopic compositions (70% or 97% 239Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multinucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO2-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% 239Pu than for 70% 239Pu.     

Effect of a pulsed magnetic field on tumoral C3H/Bi female mice

Female C3H/Bi mice develop spontaneous viral mammary carcinoma which can metastasize to the lungs. Two hundred and forty tumoral mice were either exposed to a toro?dal pulsed magnetic field, 12 Hz, 100 Hz or 460 Hz in frequency or used as controls. The exposure was mainly done 10 min. a day, 3 days a week, or 30 minutes once a week from about 2 to 3 weeks after the appearance of the tumors until death. In comparison with the controls, the exposed mice showed lighter spleens and lungs; this last observation could mean fewer pulmonary metastases. The weight of the tumors has been found lighter for 460 Hz MF, not changed for 100 Hz MF, heavier for 12 Hz MF, but lifespans were not altered by the exposure.