The spatial and temporal distribution of inhaled UO2 particles in the respiratory tract of the rat. I. Pulmonary tissue.

An analysis is described of the mass distribution of inhaled UO2 particles in the pulmonary tissue of rats by random sampling of fields in autoradiographs of histological sections. The degree of nonrandomness is compared between fields, between sections, and between lobes and interpreted in terms of the physical distribution of UO2. The error in the estimate of the mean number of charged-particle tracks from UO2 per field in the pulmonary tissue by selective tissue sampling is related to the degree of nonrandomness of the UO2 distribution. Estimates of this error in the lungs from nine animals range from 5.2 to 8.4%. When estimating this error, it is concluded that, in the case of the rat, sections should be taken at intervals of 3 mm or less throughout the lobes.

The spatial and temporal distribution of inhaled UO2 particles in the respiratory tract of the rat. II. The relative concentration of UO2 between the intrapulmonary airways and the pulmonary tissue.

In this experiment the relative masses of UO2 particles per unit mass of tissue are determined between intrapulmonary airways and pulmonary tissue in rat lungs. A mean value of 0.57 +/- 0.06 (SE) was determined in tissue sections taken at 3-mm or 5-mm intervals throughout the lobes of animals killed from 2 to 35 days after inhalation. The experimental results are compared with data derived from the ICRP Lung Model for man and indicate that in the rate approximately 4% of the lung burden as opposed to about 0.02% derived for man is associated with the intrapulmonary airways. The 4% figure, if also applicable to man, would have extremely important implications in radiological protection, since the basal cells of the bronchial epithelium are thought to be sensitive to the induction of bronchogenic carcinoma.

Alpha and fission fragment autoradiography with superimposed tissue images in CR-39 plastic.

A technique is described by which the distributions of both fissionable and alpha-emitting radionuclides in histological sections of lung are visualised in the nuclear track recording plastic CR-39. Fission fragments and alpha-particles from radionuclides contained within the section register as tracks in CR-39 and an image of the tissue structure is induced, superimposed upon the track distribution, by means of low-energy (less than 1 MeV) alpha-particles from an external 238Pu source. Thus accurate apposition of the track distribution and tissue structure is achieved. The efficiencies of this system for alpha-particle and fission fragment detection are 0.51 +/- 0.09 (SD) and 0.48 +/- 0.08 (SD) respectively.

The carcinogenic effect of localized fission fragment irradiation of rat lung.

In a preliminary investigation of 'hot particle' carcinogenesis uranium oxide particles were introduced into the lungs of rats either by intubation of a liquid suspension of the particles or by inhalation of an aerosol. Subsequently the animals were briefly exposed to slow neutrons in a nuclear reactor, resulting in localized irradiation of the lung by fission fragments emitted from 235U atoms in the oxide particles. The uranium used in the intubation experiments was either enriched or depleted in 235U. Squamous cell carcinomas developed at the site of deposition of the enriched uranium oxide in many cases but no lung tumours occurred in the rats with the depleted uranium oxide, in which the lung tissue was exposed to very few fission fragments. Only enriched uranium oxide was used in the inhalation experiments. Pulmonary squamous cell carcinomas occurred after the fission fragment irradiation but were fewer than in the intubation experiments. Adenocarcinomas of the lung were seen in rats exposed to uranium oxide without subsequent irradiation by neutrons in the reactor and in rats irradiated with neutrons but not previously exposed to uranium oxide. It is concluded that (i) fission fragments were possibly implicated in the genesis of the squamous cell carcinomas, which only developed in those animals exposed to enriched uranium oxide and neutrons and (ii) the adenocarcinomas in the rats inhaling enriched uranium oxide only were likely to have been caused by protracted irradiation of the lung with alpha-rays emitted from the enriched uranium.

The distribution and clearance of inhaled UO2 particles on the first bifurcation and trachea of rats.

The distribution of inhaled UO2 particles is described in the upper respiratory tract of rats up to 14 d after inhalation. Delayed neutron analysis was used to determine accurately nanogram quantities of UO2 present in excised tissues. The mass of UO2 in the extrapulmonary bronchi and first bifurcation decreased more slowly over 0--8 d after inhalation than the corresponding mass on the trachea. Between 8 and 14 d neither amount altered significantly. Small but significant quantities of UO2 deposited on the trachea during inhalation, remained until at least 14 d after inhalation.

The distribution and clearance of inhaled uranium dioxide particles in the respiratory tract of the rat.

The distribution and clearance of inhaled UO2 particles in the respiratory tract of the rat has been determined by track counting in histological sections of lung at various times after a single brief inhalation. The results do not agree with the I.C.R.P. lung model. An alternative model is proposed which is more consistent with the data.