Analysis of lung tumour risk in radon-exposed rats: an intercomparison of multi-step modelling.

Three carcinogenesis modelling groups have both jointly and separately applied a multi-step carcinogenesis model with clonal expansion to one data set of lung tumours in rats exposed to radon (CEA, France). This study was designed to investigate the differences in modelling approach and fitting procedures used by the three groups in detail, and to explore possible discrepancies in the results. Using the same model assumptions and a (linear) radiation dependence on the first model step only, the three groups arrived at identical best fits, proving that the mathematical formalisms and fitting procedures do not lead to different results.

Neutron RBE for induction of tumors with high lethality in Sprague-Dawley rats.

The effectiveness of fission neutrons is compared to that of gamma rays and X rays with regard to the induction of malignancies in male Sprague-Dawley rats. The analysis is based on autopsy results. It is focused on tumors that tend to be present in animals dying early, which is indicative of a high degree of lethality.

Carcinogenic and cocarcinogenic effects of radon and radon daughters in rats.

It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners.

[Experimental study of different histologic types of pulmonary cancers induced by irradiation].

Recent epidemiologic studies suggested that some histologic types of carcinomas were preferentially induced in the lung by irradiation, whatever the mode of exposure and the radiation quality. Since smoking and other environmental airborne pollutants may be strong confounding factors in humans, we have investigated whether histological subtypes were dependent or not on the mode of exposure, in a large series of 9000 rats exposed to external and internal sources at high and low Linear Energy Transfer. Despite comparable overall risk coefficients in rats and humans, our results show that histological types are influenced not only by dose but also by radiation quality and heterogeneity of dose delivering.

[Importance of the role of dose rate on tumor induction in rats after radon inhalation].

Lung cancer can be induced in rats, by radon daughter products, after exposure as low as 25 WLM (80 mJ.h.m-3) protracted over 4 to 6 months with a dose rate of 100 to 150 WL (2 to 3 mJ.

[Role of age at the moment of irradiation on the induction of tumors].

The probability that rats develop tumours following a 3 Gy exposure to gamma rays from cobalt 60 was observed to depend on age at exposure. Lifetime excess of neoplasia decreased by a factor of about 10 in 9-month-old rats as compared to animals irradiated in utero. The 3-month age group developed slightly fewer tumours than the group irradiated in utero, and tumour location was different.

[Carcinogenic effects of low-dose gamma ray irradiation].

For a dose of 3 Gy delivered by cobalt 60 gamma rays on rats, a reduction of the dose rate by a factor of 60 decreased the carcinogenic effectiveness by a factor of about 5. This decreased effect was essentially observed for carcinomas.

Lung carcinomas in Sprague-Dawley rats after exposure to low doses of radon daughters, fission neutrons, or gamma rays.

The effectiveness of radon-daughter inhalation and irradiation with fission neutrons and gamma rays in the induction of lung carcinomas in Sprague-Dawley rats at low doses is compared. Earlier reports which compared radon-daughter inhalations and neutron irradiations over a wider range of doses were based on dosimetry for the radon-daughter inhalations which has recently been found to be faulty. In the present analysis, low-dose experiments were designed to derive revised equivalence ratios between radon-daughter exposures, and fission neutron or gamma irradiations.

Comparison of the induction of pulmonary neoplasms in Sprague-Dawley rats by fission neutrons and radon daughters.

Pulmonary carcinomas were recorded in a life-span experiment of male Sprague-Dawley rats exposed to fission neutrons. Mortality-corrected prevalences are obtained by the method of isotonic regression. In a second part of the paper a comparison is made with data obtained earlier for radon-daughter inhalations in the same strain of rats.

Metabolism of plutonium introduced as Tri-N-Butylphosphate complex in the rat and removal attempts by DTPA.

The metabolism of plutonium introduced as the Pu-Tri-N-Butylphosphate complex (Pu-TBP) was studied in rats after inhalation, injection and ingestion. Early translocation and distribution of 239Pu in organs for 30-400 days after inhalation exposure are presented. The tracheobronchial clearance was impaired at early times, followed from about one week by clearance from the deep lung as characterized by a half time of 100 days.

Incidence of various types of thoracic malignancy induced in rats by intrapleural injection of 2 mg of various mineral dusts after inhalation of 222Ra.

After inhalation of 222Ra at equilibrium with radon daughters, male Sprague-Dawley rats were inoculated intrapleurally with 2 mg of unleached or acid-leached asbestos fibres or glass fibres or quartz. The additive co-carcinogenic effects of this type of insult were demonstrated by the increased incidence of malignant thoracic tumours. In rats given mineral materials, bronchopulmonary carcinomas and mixed carcinomas were observed, as well as typical mesotheliomas and combined pulmonary pleural tumours, whereas in control rats inhaling radon alone, only bronchopulmonary carcinomas occurred.

Characterization of a major natural killer activity in rat lungs.

A high level of antitumoral cytotoxicity was observed in the lymphoid population extracted by perfusion from lung capillaries. The in vitro cytotoxicity against tumor cells was demonstrated with the murine lymphoma YAC-1 cells or with the syngeneic P 77 rat lung fibrohistiocytoma cells. It was demonstrated that this cytotoxic activity had the characteristics of natural killer activity.

Mesotheliomas in rats following inoculation with acid-leached chrysotile asbestos and other mineral fibres.

The carcinogenicity of untreated UICC chrysotile A, of acid (oxalic and hydrochloric)-leached UICC chrysotile A, of crocidolite and of JM 104 glass fibres has been studied by intrapleural injection into rats. This experiment, carried out on 304 animals, demonstrated that when more than 80% of the Mg had been leached from chrysotile fibres by either hydrochloric or oxalic acid, the proportion of pleural mesotheliomas was either nil or dramatically lower than that obtained with untreated chrysotile. The carcinogenic effect of crocidolite was higher than that of 43.

Malignant bone tumours induced by a local injection of colloidal radioactive 144Cerium in rats as a model for human osteosarcomas.

Lung metastases were observed in 80% to 85% of rats bearing advanced malignant bone tumours (osteogenic osteosarcomas and angiosarcomas). These tumours were induced in 2-month-old Sprague-Dawley rats by inoculation of a colloidal suspension of radioactive cerium (144Ce) into the hind leg, in close contact to the bones of the knee joint. Twenty-eight rats were killed or died spontaneously shortly after detection of palpable tumours at the site of injection: the incidence of lung metastases was 73.

SO2-induced bronchopathy in the rat: abnormal permeability of the bronchial epithelium in vivo and in vitro after anatomic recovery.

The effects of different SO2 exposures on the uptake and transport of exogenous proteins by the tracheobronchial epithelium were investigated in vivo and in vitro using explanted tissue from rat lungs. By optical and electron microscopy, modifications in ferritin uptake and transport were observed, depending on SO2 exposure and on subsequent structural changes; these changes involved a considerable increase in mucosal permeability, both in vivo and in vitro, affecting the epithelium of the trachea and main bronchi. Such an increase, although reduced, was observed 3 months after SO2 exposure had been discontinued, at a time when the structure appeared normal.

Bone tumours induced in rats with radioactive cerium.

A technique is described for the induction of metastasizing bone tumours in rats by local inoculation of 144cerium. Bone sarcomas develop in 90% of the animals and 74% of these had lung metastases. The tumours can be easily cultured and maintained by serial transplantations.

Mesothelioma induced by intrapleural injection of different types of fibres in rats; synergistic effect of other carcinogens.

Intrapleural injections of 20 mg of various mineral fibres were made to rats. Three types of fibres (chrysotile, crocidolite and glass fibres) were untreated; other chrysotile fibres were leached to different degrees. The results show that chrysotile is the most toxic of the three: animals died sooner and presented mesotheliomas earlier.

[Fibre interaction with red blood cells or alveolar macrophages "in vitro" (author's transl)].

Haemolytic activities and effects on alveolar macrophages (AM) of various fibres were studied. UICC asbestos fibres and attapulgites either untreated or acid-leached were used. Amphiboles and commercial attapulgites were both cytotoxic on AM, but attapulgites and chrysotile were only haemolytic.