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The effects of acute and chronic doses of morphine on intracellular levels and distribution of catecholamines (CA) were studied in the rat. Brain homogenates were fractioned into crude synaptosomal pellets and supernatants. The synaptosomes were osmotically shocked, and dopamine (DA) and norephinephrine (NE) levels were measured as bound (synaptic vesicles), free (extravesicular), and extrasynaptosomal fractions in the supernatant. The rate of synthesis of CA was determined by estimating conversion of injected CC14) tyrosine into CC14) DA and CC14) NE. Acute injections of morphine (60 mg/kg body weight) resulted in significant increases in the extrasynaptosomal and free fractions of NE. An increase in endogenous levels of DA was seen in the extrasynaptosomal CC14) DA at 30 and 60 min respectively. The bound fractions demonstrated no appreciable differences at any of the testing intervals. In chronically treated rats, endogenous extrasynaptosomal levels of both DA and NE were higher than in controls, while only NE was increased in the free fraction. These data are consistent with a morphine-induced increase in the biosynthesis of DA and NE, resulting in increased levels of NE in the nonfunctional storage pools rather than in the more readily available pools. This is supported by the lack of change in the levels of the bound fraction suggesting preferential release of newly synthesized NE followed by replenishment due to increased synthesis. These conditions could result in constant equilibration of the bound fraction.

The specific objectives of this study were (1) to determine to what extent cell turnover (reproduction) effects the difference in radiation sensitivity of the individual cell types, and (2) to investigate the relationship which exists among the cell types during the damage and recovery period. Six hundred and seventy-two rats were exposed to either of the two radiation sources and sacrificed at periodic intervals following exposure for the purpose of determining the change in numbers of cells in the marrow. The results indicate that the difference in the response of the individual types of cells is not directly related to their turnover rate. The turnover rate for the myelocytic cells is greater than the turnover rate for the erythrocytic cells, yet the erythrocytic precursor cells are more sensitive to radiation than the myelocytic precursor cells. The results also show that erythrocytic cells recover before myelocytic or lymphocytic cells. This recovery indicates that lymphocytic cells probably could not give rise to the other two cell types (function as a stem cell) through a process of differentiation or dedifferentiation. However, it may be possible that the lymphocytic cells could function as trephocytes.

Sprague-Dawley rats were subjected to a whole-body dose of 15 krads of mixed gamma-neutron radiation. At 2 and 24 hours following irradiation 14 animals from the irradiated group and 14 unirradiated controls were sacrificed by replacing the blood in the brain circulation by perfusion with a sucrose-eserine solution. The medulla section of the brain was removed, homogenized and prepared for ultracentrifugation and sucrose density gradient separation. The separated synaptic vesicles were assayed for protein and acetylcholinesterase (ACHE). A decrease in protein was found 2 hours after irradiation with a greater decrease 22 hours later. A decrease in ACHE activity was also seen 2 hours after irradiation but there was no further decrease at 24 hours. These results were correlated with vascular changes found during the central nervous system (CNS) syndrome. (Author)

A biochemical analysis for acid phosphatase was made of soluble protein and lysosomes in liver cells of rats exposed to 2 krads of x rays. The results clearly showed an increase in the acid phosphatase activity in the lysosomes and in soluble protein 2 hours after exposure. This was followed by a decrease in enzyme activity in the lysosomes and a consistent high level in the soluble protein. The results correlated well with earlier cytochemical studies and showed that, in addition to the radiation-induced increase in number and size of lysosomes, there is a distinct increase of acid phosphatase in the lysosomes themselves. This substantiated earlier findings. In addition, the persistent high level of acid phosphatase in the soluble protein (cytoplasm) was a possible indication of early radiation impairment of the lysosomal membrane. (Author), See also Report dated Dec 69, AD-701 756.

Ultrastructural and biochemical changes in lysosomes of rat liver following exposure to ionizing radiation were studied. A marker for acid phosphatase was used to visually correlate the progressive changes in lysosomes with the cellular necrobiotic process postirradiation. The earliest observable change in the lysosomes and/or lysosomal enzymes corresponding with the sequence of fine structural alterations following irradiation suggests that radiation labilizes the lysosomal membrane resulting in a release of enzymes responsible for cell damage. The concentration of the lead phosphate reaction product indicated that the initial action on the lysosome is evidently a 'build-up' of hydrolytic enzymes within 2 hours after irradiation followed by a gradual release of the marked enzyme 2-24 hours postirradiation as noted by decreased enzyme concentration within the lysosomes. The release of the enzyme appeared to be directly related to an increasing cellular necrobiosis following irradiation. (Author)

Sprague-Dawley rats were subjected to a whole-body dose of 15 krads of mixed gamma-neutron radiation. Following irradiation, the animals were intravenously injected with horseradish peroxidase (HRP) and sacrificed. The medullae of these animals were fixed either by perfusion or by immersion, incubated in a substrate medium and processed for electron microscopic examination. In control animals subjected to the same procedures, the reaction product of the enzyme HRP and its substrate was confined to the lumina of the blood vessels in the brain fixed by immersion and completely washed out of the blood vessels of the brain fixed by perfusion. The brain tissue of the irradiated animals injected with HRP and fixed by immersion exhibited a dense reaction product in the lumina of the blood vessels, in invaginations of the luminal surface, and in micropinocytotic vesicles of the endothelial cell cytoplasm. The most significant alteration in the medullary tissue of the irradiated animals was an increase in the number of micropinocytotic vesicles in the endothelial cells. It appears, then, that damage caused by high doses of radiation initiates increased vascular permeability which may lead to the edematous condition observed in the irradiated animal. (Modified author abstract)