Edward P. Radford

Polonium-210: A Volatile Radioelement in Cigarettes.

Polonium-210, which emits alpha particles, is a natural contaminant of tobacco. For an individual smoking two packages of cigarettes a day, the radiation dose to bronchial epithelium from Po210 inhaled in cigarette smoke probably is at least seven times that from background sources, and in localized areas may be up to 1000 rem or more in 25 years. Radiation from this source may, therefore, be significant in the genesis of bronchial cancer in smokers.

Radon-exposed underground miners and inverse dose-rate (protraction enhancement) effects.

Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern. That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, we evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data. There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose. As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose. Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution.

Distribution of Polonium 210 in Pulmonary Tissues of Cigarette Smokers.

Concentrations of the alpha-particle-emitting radioactive element polonium was measured in various pulmonary tissues of smokers and nonsmokers in order to determine 1) whether this radiation exposure is associated with the development of bronchial cancer in smokers; and 2) how smoke is absorbed and excreted in human lungs. Lung specimens from 25 current cigarette smokers, 2 current pipe smokers, 1 former cigarette smoker, and 8 nonsmokers ere analyzed. The average concentration of polonium in the peripheral parenchyma of current smokers was .0074 picocurie/gm and in nonsmokers was .0016. For smokers, the average concentration was doubled in more centrally located parenchyma and was greater in the upper than in the lower lobes. Polonium concentrations correlated with daily cigarette consumption but not with total cigarettes smoked. The concentrations in peribronchial lymph nodes of smokers were also higher than in nonsmokers. These values show no correlation with total or daily cigarette consumption. Polonium concentration was similiar in bronchial wall parenchyma as in lung parenchyma but was greater in bronchial epithelium than in parenchymal or lymph nodes. The patterns of distribution of polonium throughout the lung suggest that most inhaled smoke particles are rapidly cleared from the lung, and polonium is primarily cleared by mucus sheet. Since the highest local concentrations of polonium were found in bronchial epithelium from segmental bifurcations, leading to a high cumulative local radiation dose, polonium may be implicated in the initiation of bronchial cancer in humans.

Method for Estimating Respiratory Surface Area of Mammalian Lungs from Their Physical Characteristics.

The surface area available for gas exchange in the lungs s an impotant factor in gas transfer between the alveoli and the blood 1 ., 2 Present estimates of this area are based on measurements of alveolar dimensions taken from fixed histologic specimens 3 , 4 , 5 . These estimates of total surgace area are made by measuring or calculating the area/volume ratio for a small portion of lung tissue and applying this ratio to an assumed total lung volume. The volume which must be assumed is uncertain because the degree of inflation represented in the particular specimen is difficult to determine, especially if the lungs are allowed to collapse before fixation is complete. Moreover, distortion of lung architecture inevitably occurs with standard histologic methods involving dessicatin and embedding, and such lobular subdivisions as the air-sacs and alveolar ducts, which contribute only slightly to the respiratory surface area, have in the inflated state a much larger volume than is generally realized 6 . for these reasons calculation by anatomic methods tend to result in overestimating the number of alveoli and the total lung surface. The method of estimating lung surface described in this report is based on physical measurements of the lungs and avoids any assumption of size or configuration of respiratory structures. The calculation depends on consideration of the changes in free energy of the lungs as they are deflated. During inflation, energy is stored by deforming elasitc elements. and by the creation of a large air-liquid interface If the lungs are diflatd by allowing volume equilibrium at successive pressure decrements, the stored energy released during deflation can be measured.

Human Health Effects of Low Doses of Ionizing Radiation: The BEIR III Controversy

Controversy in the BEIR III Subcommittee on Somatic Effects concerning human health effects of low doses of low-LET radiation has centered on (a) the appropriate dose-response relationship by which extrapolation to low doses of data obtained at relatively high doses should be governed, and (b) the appropriate human evidence which should be the basis of estimation of lifetime cancer risk from radiation exposure. It is shown that the use of the linear no-threshold dose-response relationship for extrapolation purposes is an excellent approximation that is in agreement with widely accepted fundamental radiobiological principles. The appropriate human data for derivation of cancer risks are the composite age-specific risks derived from all epidemiologic studies of human cancer resulting from partial-body and whole-body radiation exposure; this composite is in good agreement with the currently available cancer incidence dose-response data obtained from the Nagasaki Tumor Registry. The current version of BEIR III significantly underestimates the radiationinduced cancer risk because it ignores the effect of high-dose-rate, low-LET radiation on cell survival in relation to cancer induction probability, and because it emphasizes cancer mortality rather than cancer incidence. Use of the appropriate basis of risk estimates gives a lifetime cancer risk per rad per million persons exposed of 260 to 880 excess incident cases for males, and 550 to 1620 excess cases for females. This result is about five times higher than the values given in the current version. Rossis contention that the appropriate relationship is that the carcinogenic effect of radiation is proportional only to dose squared is contrary to the majority of current theoretical, experimental, and epidemiological evidence. The controversy and the way in which it was resolved raises important questions about how the public and its representatives can in the future obtain objective scientific evaluations of issues that may have significant economic, social, and political implications.

COMPARISON OF CONCENTRATIONS OF ALPHA-EMITTING ELEMENTS IN TEETH AND BONES.

SummaryTo evaluate the suitability of teeth as indicators of the skeletal burden of alpha-emitting elements, variability of content of 226Ra, 210Pb, and 228Th has been determined: (a) for different teeth from the same individual, and (b) between tooth levels and the amount in bone samples from the iliac crest in the same individual.There was a significant correlation between the levels of 210Pb and 226Ra in teeth compared with iliac crest, supporting the conclusion that teeth are adequate samples to estimate human skeletal burdens of these alpha-emitting elements.Preliminary results are given indicating that local variations within individual bones or teeth may be considerable; thus any small sample of calcified tissue may be an inadequate indicator of total-body burden. Even so, teeth are as satisfactory as small bone fragments for comparing levels in groups of human subjects.

CIRCULATING ANTIDIURETIC HORMONE IN THE X-IRRADIATED RAT.

Male rats exposed to 500 R of whole-body x-irradiation were allowed food and water ad libitum and housed in metabolism cages; water and food intake and urinary and fecal excretion were recorded daily. Urine output increased 200% during the first 24 hours after irradiation. No significant changes occurred in daily sodium, potassium, urea, or total solute excretion, although calcium excretion approximately doubled after irradiation. The marked increase in free water excretion implicates antidiuretic hormone (ADH) in this phenomenon. Application of a sensitive bioassay for ADH permitted measurement of plasma ADH concentrations in undisturbed, unanesthetized rats before and after irradiation. ADH levels were lower and frequently not detectable 24 hours after exposure. High ADH levels, however, could be provoked in irradiated rats by hemorrhage, indicating that the receptor cells and secretory ability of the posterior pituitary remained intact. Furthermore, irradiated rats responded normally to small intravenous injections (4 to 8 microU) of exogenous ADH. Rats with congenital diabetes insipidus given daily injections of Pitressin showed no postirradiation diuresis. Lastly, increased urinary calcium excretion may result from hypercalcemia which is known to induce diuresis through calcium-vasopressin antagonism. These results further suggest that the diuretic response is due to decreased circulating ADH.

Interrelationships between water and electrolyte metabolism in rats

Abstract I have discussed the regulation of water balance by normal adult rats in relation to electrolyte turnover. The evidence presented supports the view that endogenous ADH is normally maintained at a level sufficient to keep urine water close to the minimum, and that ADH may have an additional effect of inhibiting water intake. The normal antidiuresis of rats could be largely abolished by feeding a sodium-, potassium- and chloride-free diet. The significance of a dependence of ADH production on electrolyte intake, in relation to the idea that ADH may be one stimulus of ACTH production, has been discussed briefly. Preliminary work on spontaneous renal disease in old rats indicates an influence of acid-base balance of the diet on functional changes observed in these animals.