Radioactive nitrogen-13 from nitrite (NO2-) or nitrate (NO3-) administered intratracheally or intravenously without added carrier to mice or rabbits was distributed evenly throughout most organs and tissues regardless of the entry route or the anion administered. Nitrogen-13 from both anions was distributed uniformly between plasma and blood cells. We found rapid in vivo oxidation of NO2- to NO3- at concentrations of 2 to 3 nanomoles per liter in blood. Over 50 percent oxidation within 10 minutes accounted for the similar nitrogen-13 distributions from both parent ions. The oxidation rates were animal species-dependent. No reduction of 13NO3- to 13NO2- was observed. A mechanistic hypothesis invoking oxidation of 13NO2- by a catalase-hydrogen peroxide complex accounts for the results. These results imply a concentration dependence for the in vivo fate of NO2- or nitrogen dioxide.
One of two topics explored is the limitations of the daily average in summarizing pollutant hourly profiles. The daily average of hourly measurements of air pollutant constituents provides continuity with previous studies using monitoring technology that only provided the daily average. However, other summary statistics are needed that make better use of all available information in 24-hr profiles. The daily average reflects the total daily dose, obscuring hourly resolution of the dose rate. Air pollutant exposures with comparable total daily doses may have very different effects when occurring at high levels over a few hours as opposed to low levels over a longer time.
Analysis of lifetime studies of 243 beagles with skeletal burdens of radium-226 shows that the distribution of bone cancers clusters about a linear function of the logarithms of radiation dose rate to the skeleton and time from exposure until death. Similar relations displaced by species-dependent response ratios also provide satisfactory descriptions of the reported data on deaths from primary bone cancers in people and mice exposed to radium-226. The median cumulative doses (or times) leading to death from bone tumors are 2.9 times larger for dogs than for mice and 3.6 times larger for people than for dogs. These response ratios are well correlated with the normal life expectancies. The cumulative radiation dose required to give significant risk of bone cancer is found to be much less at lower dose rates than at higher rates, but the time required for the tumors to be manifested is longer. At low dose rates, this time exceeds the normal life-span and appears as a practical threshold, which for bone cancer is estimated to occur at an average cumulative radiation dose to the skeleton of about 50 to 110 rads for the three species.
A total of 66 primary bone sarcomas were diagnosed in 47 beagles; 43 of these dogs were part of the 403 beagles fed 90Sr and 4 were part of the 162 controls. Multiple primary bone sarcomas were found in 15 of the 47 beagles (32%). The incidence of multiple primary bone sarcoma was restricted to the two highest dose groups, except for a single control dog which developed two bone sarcomas. A threshold-like radiation dose response was observed; no sarcomas were observed in the lowest three dose groups, but the number of primary bone sarcomas increased rapidly in the higher dose groups. Of the 66 primary sarcomas, 49 were osteosarcomas (74%). As the dose increased, the proportion of osteosarcomas increased sharply, 4/10 (40%), 26/29 (90%), and 16/18 (89%), in the three highest dose groups. Thirteen of the bone sarcomas of other types occurred in males, and 4 in females, whereas 21 osteosarcomas occurred in males, and 28 in females. The ratio of bone sarcomas of the appendicular skeleton to those in the axial skeleton was 40:26, with osteosarcomas occurring more often in the appendicular than the axial skeleton (32:17), whereas nonosteogenic tumors showed no predilection (8:9). A statistical study of the distribution of bone sarcomas among 16 separate bone groups showed a correlation only with the distribution of cancellous bone volume-to-surface ratio and not with either skeletal mass distribution or dose distribution. The highest occurrence of sarcomas was in the humeri, femora, and mandible, and no occurrence in the coccygeal vertebrae, paws, or sternum. It is postulated that the distribution of bone sarcomas reflects a critical combination of the osteosarcoma precursor cell population, their cell division rate, and the radiation dose absorbed by these cells.
The whole-body clearance, organ distribution, and subcellular distribution of no-carrier-added and carried-added intraperitoneally administered bismuth radiotracers (205Bi-206Bi) has been determined in Sprague-Dawley rats. Differences in clearance rate kinetics were observed for this study with the administration of neutral solutions of tracers in a carbonate buffer compared to other studies with other chemical forms. The final organ distribution was not strongly dependent on administered chemical form. We provide definitive evidence that bismuth does indeed enter subcellular organelles such as the nucleus and the mitochondria, which had 30-50% and 10-25%, respectively, of activity in kidney tissue. The kidneys were the main sink for radiotracer with uptake ranging from 20 to 50% of total body activity. The calculated energy deposition by recoil nuclei after alpha emission of potentially therapeutically useful 212Bi was found to equal or exceed the alpha energy deposition per organelle if the source is inside the cell nucleus or mitochondria.
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