P. Fritsch

Co-carcinogenic effects of various agents in rats following exposure to radon and radon daughters

Abstract Combined exposure to radon and to various occupational or environmental airborne pollutants may lead to synergistic effects for lung cancer induction. Experimentally, a co-carcinogenic effect results in increased tumour incidence after combined administration of the potential carcinogens. This paper is a review based on a standardized protocol developed to identify potential co-carcinogenic agents, using an in vivo model in rats. Rats were exposed to 3.6 J h m −3 (1000 WLM) of radon, followed by exposure to the agent to be studied. Different types of compounds were studied, including chemicals, mineral particles and fibres, and diesel exhaust particulates. The greatest synergistic effects were observed after administration of chemical compounds known to be cytochrome P-450 1A1 inducers which are metabolized to mutagenic or non-mutagenic forms. The results observed after treatment by cytochrome P-450 1A1 inducers indicated that radon exposure seems to specifically increase early proliferation of target cells during the co-carcinogenic process. Combined exposure to radon and tobacco smoke resulted in a multiplicative synergistic effect. For the same cumulative radon exposure, the incidence of lung carcinomas increased with the cumulative exposure to tobacco smoke. Intrapleural injection of various mineral fibres following exposure to radon resulted only in an additive co-carcinogenic effect, whereas intratracheal instillation of different minerals associated with metallic mine ores did not result in significant synergistic effects. Under the experimental conditions used, no synergistic effect was observed after combined exposure to radon and diesel exhaust.

Epithelial cell migration on small intestinal villi in the neonatal rat. Comparison between [3H] thymidine and cytoplasmic labelling after Pu-citrate ingestion

This study compares, in 2‐d‐old rats, the migration rates of epithelial cells on villi of the small intestine, using two labelling methods: a single [3H] thymidine injection; and cytoplasmic labelling by a single ingestion of Pu‐citrate. Histoautoradiography shoed negligible diffusion of Pu after the initial retention, which was mostly confined to the epithelial cells of the villi. However, after sloughing of labelled cells in the intestinal lumen, Pu was reabsorbed by the distal epithelial cells. In segments in which Pu reabsorption was negligible, the migration rates of Pu‐ and 3H‐labelled cells were very close. These rates, expressed in micrometers, were almost constant along the length of the villus, and the Pu and 3H labelling edges reached the top of the villi in about 5 and 7 d, respectively.

Histological study of retinal damages induced by multiple picosecond pulses

The current laser safety standards do not define the exposure limit values for pulsewidth less than one nanosecond. It has been hypothesized that one cannot extrapolate from longer pulse widths because the ultrashort pulse contains high peak power and may induce non linear effects. These effects may involve fundamentally different mechanisms of damage particularly for repetitively ultrashort pulses1. Most laser safety documents advise the laser user that caution must be used in the evaluation of exposure to repetitively pulsed radiation since they are only limited data on multiple pulse exposure criteria. The empirical multiple pulse formula is based on some data indicating that there is generally a cumulative effect in multiple-pulse exposures. No data exists in the litterature concerning the histological effects on the retina of ultrashort pulses delivered with a high repetition rate.The current laser safety standards do not define the exposure limit values for pulsewidth less than one nanosecond. It has been hypothesized that one cannot extrapolate from longer pulse widths because the ultrashort pulse contains high peak power and may induce non linear effects. These effects may involve fundamentally different mechanisms of damage particularly for repetitively ultrashort pulses1. Most laser safety documents advise the laser user that caution must be used in the evaluation of exposure to repetitively pulsed radiation since they are only limited data on multiple pulse exposure criteria. The empirical multiple pulse formula is based on some data indicating that there is generally a cumulative effect in multiple-pulse exposures. No data exists in the litterature concerning the histological effects on the retina of ultrashort pulses delivered with a high repetition rate.

ENERGY DISPERSIVE X-RAY SPECTROMETRY IN THE ENTIRE ALVEOLAR MACROPHAGE, A TOOL TO CHARACTERIZE THE CHEMICAL COMPOSITION OF PARTICLES DEPOSITED IN THE DEEP LUNG AFTER INHALATION

The aim of this study was to develop a method to characterize the physico-chemical properties of inhaled particles in alveolar macrophages of rats and primates extracted by pulmonary lavage, by observing the entire cells using electron microscopy. The optimal conditions for identification of phagocytosed particles were dark-field STEM at 200 kV and then energy dispersive X-ray spectrometry was performed. This technique using CdS and mixed (U, Pu) oxide aerosols was applied to rats which were examined a few days after exposure and using U3O8 aerosols on primates which were examined four years after exposure. The method is capable of determining the shape, size, and chemical composition of particles deposited in the deep lung after inhalation. Characterization of the heterogeneity in the chemical composition of particles can be performed in a size of 20–30 nm. Some limitations have been encountered, however, especially for particles containing elements present in the biological matrix such as P.

Deposition of 214Pb and nuclear aberrations in the respiratory tract of rats after exposure to radon progeny under different aerosol conditions

Abstract The aim of this work was to relate 214 Pb deposition within the respiratory tract of the rat to aerosol characteristics during exposure to radon and its progeny. Two different exposure conditions were studied: static, without air recirculation with a low unattached fraction of radon progeny ( fp ≈10%); and dynamic, with continuous air recirculation ( fp >80%). Deposition was estimated by measuring 214 Pb retention in nasopharynx and lungs at the end of a 3-h exposure using gamma spectrometry. The deposition of 214 Pb in the pulmonary region was the same in the two exposure conditions. By contrast, nasopharynx deposition was 5 times higher under dynamic than under static exposure. The dose delivered to the deep lung was estimated by micronuclei scoring in alveolar macrophages extracted by pulmonary lavage. For a similar cumulative dose delivered under static or dynamic conditions, a similar micronuclei index was measured, 1.22% ± 0.26 and 1.47% ± 0.42, respectively, 8 d after exposure. These results suggest that the unattached fraction did not influence radon progeny deposition and the resulting delivered dose in the deep lung of the rat.

Evolution of sister-chromatid exchanges (SCE) in rat bone marrow cells as a function of time after 2 Gy of whole-body neutron irradiation

We scored sister-chromatid exchanges (SCE) in bone marrow cells in 3-month-old rats as a function of time after 2 Gy of whole-body neutron irradiation. This dose reduced the mean survival time to 445 days after irradiation, and induced more than one tumor per animal; by 200 days post irradiation, all animals bore tumors at autopsy, but bone marrow was not a significant target for tumor induction. In controls, the mean SCE/cell remained constant from 3 to 24 months of age (2.38 SCE/cell, S.D. = 0.21). Irradiation induced 2 distinct increases in SCE: the first occurred during the days following exposure, and the second, from days 150 to 240. Thereafter, SCE values formed a plateau at 3.37 SCE/cell (S.D. = 0.39) until day 650. Between the two increases (i.e. from days 15 to 150), SCE dropped to control values. Analysis of SCE distribution per cell shows that the entire dividing cell population altered homogeneously during the increase in SCE. These results suggest that in our irradiated rats, the second increase in SCE coincides with tumor growth, whereas the first increase might be due to DNA damage that was rapidly repaired.