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Biomedical subjects

R Masse

Publications and source records attributed to R Masse.

At least 55 records · Page 3Linked to original sources

Early modifications of outgrowth and metallo-endopeptidase activity in fibroblasts from rat cutaneous explants after local gamma-irradiation: dermis cellularity and collagen fibre alterations.

The initial response to local gamma-irradiation of skin was investigated in fibroblasts from cutaneous explants after doses of 4, 8, 12, 16 or 20 Gy. On the day of irradiation, fibroblast outgrowth was inhibited in a dose-dependent manner, but by day 7 post-irradiation, cell restoration occurred especially in explants exposed to 4 or 8 Gy. The dose-dependent inhibition of fibroblast outgrowth correlated with the decrease in cellular metallo-endopeptidase (MEP) activity against succinyl trialanine paranitroanilide. However, the secretion of this MEP activity was 10-fold higher in the culture medium after the lowest irradiation dose (4 Gy). Its inhibition profile was not modified after local irradiation, whatever the dose. In vivo, the cell density of mastocytes, pericytes and endothelial cells decreased after irradiation. Moreover, damaged collagen was observed in the superficial dermis after local irradiation. These results strongly suggest that this MEP may be involved in the alterations occurring in dermal connective tissue components after skin irradiation. The rapid decrease with the dose in fibroblast outgrowth and MEP activity also suggests that these two parameters may provide useful tools for dosimetric assay of the heterogeneity and extent of irradiated areas.

Aminopeptidases↗

[Experimental lung carcinogenesis. Areas of application and perspectives].

Although they have been described in several species, lung cancers are rare cancers, occurring in old age. For this reason, experimental lung carcinogenesis is practically limited to short-living rodents, rats being the most frequently used; other species have not been shown to provide improved models for extrapolation to man although they may be useful for specific toxicokinetics of some xenobiotics. The aim of experimental lung carcinogenesis is to detect putative airborne carcinogens which may cause cancer in man. Compared to man, for similar cumulated exposure, there is a general trend for a given ultimate carcinogen to result in a high rate of tumor induction in rodents; this is due to deposition and clearance patterns, together with the distal location of tumors. A weak response in rats exposed to tobacco smoke only can be easily explained by basic toxicokinetics; rats exhibit a strong response to the promoting effect of tobacco smoke. In vitro transformation of animal and human lung cells is expected to be a key issue for the purpose of interspecies extrapolation.

Animals↗

[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.

Animals↗

[Value of primates for the evaluation of pulmonary pathology].

A delicate but contrived network of tissues adapted to hematosis, handling of mediators and defense toward inhaled xenobiotics makes up the lung. Response to aggression is strongly species dependent. The primate is mostly to be used when disease modeling in animals is needed for direct extrapolation to the human. Most current field of interest includes infectious pathology, respiratory distress and toxico-kinetics modelling of aerosol hazards.

Animals↗

Risk considerations related to lung modeling.

Improved lung models provide a more accurate assessment of dose from inhalation exposures and, therefore, more accurate dose-response relationships for risk evaluation and exposure limitation. Epidemiological data for externally irradiated persons indicate that the numbers of excess respiratory tract carcinomas differ in the upper airways, bronchi, and distal lung. Neither their histogenesis and anatomical location nor their progenitor cells are known with sufficient accuracy for accurate assessment of the microdosimetry. The nuclei of sensitive cells generally can be assumed to be distributed at random in the epithelium, beneath the mucus and tips of the beating cilia and cells. In stratified epithelia, basal cells may be considered the only cells at risk. Upper-airway tumors have been observed in both therapeutically irradiated patients and in Hiroshima-Nagasaki survivors. The current International Commission on Radiological Protection Lung-Model Task Group proposes that the upper airways and lung have a similar relative risk coefficient for cancer induction. The partition of the risk weighting factor, therefore, will be proportional to the spontaneous death rate from tumors, and 80% of the weighting factor for the respiratory tract should be attributed to the lung. For Weibel lung-model branching generations 0 to 16 and 17 to 23, the Task Group proposes an 80/20 partition of the risk, i.e., 64% and 16%, respectively, of the total risk. Regarding risk in animals, recent data in rats indicate a significantly lower effectiveness for lung-cancer induction at low doses from insoluble long-lived alpha-emitters than from Rn daughters. These findings are due, in part, to the fact that different regions of the lung are irradiated. Tumors in the lymph nodes are rare in people and animals exposed to radiation. The Task Group, therefore, suggests that the total risk to the nodes cannot exceed 1/100th of the total risk to the respiratory tract, which, in turn, leads to an extremely low cancer incidence per unit dose for lymphatic tissue.

Aerosols↗

Lung dissolution of uranium tetrafluoride in rats and baboons. Comparison with dissolution by alveolar macrophages in culture and chemical dissolution.

Lung dissolution of industrial uranium tetrafluoride (UF4) was tested in rats and baboons by intratracheal instillation and inhalation, to check the W classification given to UF4 by the International Commission on Radiological Protection. Rats and baboons were given 10 and 160 micrograms of UF4 per animal respectively. Lung clearance, urinary excretion and tissue distribution of uranium were measured in rats, and urinary excretion was measured in baboons. After intratracheal instillation, daily urinary excretion was fast in both species; 4.8 +/- 0.7 X 10(-2) of the initial lung burden (ILB) in rats and 2.9 +/- 0.3 X 10(-2) in baboons. After inhalation of dry UF4 powder, daily urinary excretion was 5.6 +/- 2.2 X 10(-2) of the ILB in rats and the lung clearance half-life was 7.3 d. The amounts of uranium excreted by rats and baboons were compared to the amounts dissolved in vitro by alveolar macrophages from both species, and also to the amount dissolved chemically by a serum simulant. Both rat and baboon macrophages were clearly shown to be involved in the mechanism of uranium dissolution, since on the first day of macrophage culture, they dissolved 20 and 40% respectively of the amounts of UF4 added to the macrophage cultures, again illustrating the fast dissolution of UF4.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Intracellular localization of cerium. A microanalytical study using an electron microprobe and ionic microanalysis.

Radioactive cerium is a nuclear toxicant. Metallic cerium is used in industry. Aspects of the intracellular metabolism of this element were studied following intraperitoneal injection and aerosol exposure in rat. Two microanalytic methods, an electron microprobe and ionic microanalysis, enabled the sites of incorporation and the process of intracellular concentration of cerium to be determined in the liver, lung, kidney, bone marrow and bone tissue. The very high sensitivity of ionic analysis enabled very low concentrations of cerium to be detected with a spatial resolution of 0.5 microns. Microanalysis by electron microprobe permitted: (i) the lysosomal localization of cerium to be determined; and (ii) the lysosomal coprecipitation of cerium with phosphorus to be demonstrated. Results are discussed in relation to aspects of radiological protection.

Administration, Inhalation↗

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. The equivalence is approximately 15 working level months (WLM) of radon daughters to 10 mGy of neutrons (the earlier value was 30 WLM to 10 mGy). The relative biological effectiveness (RBE) of neutrons is 50 or more at a gamma-ray dose of 1 Gy. In these experiments with low doses and exposures, the lifetime incidences can be estimated from the raw incidences, while the derivation of the time dependence of the prevalence is essential for the estimation of RBE values and equivalence ratios.

Administration, Inhalation↗

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 showed 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. Once Pu retention had reached its maximum in 9 equal segments cut along the small intestine, tissue counting showed an exponential Pu release of 30-40%/d from each segment until the end of the experiment at d16. This constant release might reflect a constant cell migration rate during the period from Pu ingestion until d16.

Animals↗

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.

Animals↗

Localization of plutonium retention in the small intestine of the neonatal rat, guinea pig, baboon and macaca after Pu-citrate ingestion.

The retention of Pu-citrate in the gastrointestinal wall was compared at similar post ingestion times after ingestion at 2 days of age by rats and guinea pigs and at 1 to 34 days by neonatal primates. The small intestine was the main site of the Pu retention in all species. In rats and primates, most of the Pu was retained in the distal ileum, whereas in guinea pigs it was more homogeneously distributed. In the rats, Pu was retained in the epithelial cells on villi, but in the guinea pigs and primates it was confined to the macrophages under the epithelial cells in the lacteal region.

Animals↗

Pulmonary gallium uptake in rats with granulomatosis induced by complete Freund adjuvant.

To investigate the mechanism of gallium-67 uptake in lung granulomatosis, we studied 13 rats in which lung granulomatosis was induced by injection of complete Freund adjuvant (CFA) and 14 controls. Gallium uptake was assessed in bronchoalveolar lavage fluid and lavaged lung. The cells responsible for gallium uptake were identified by latent image activation autoradiography. Gallium activity in both lavaged lungs and bronchoalveolar cells (BAC) was higher in CFA-treated animals than in controls [172,205 +/- 134,783 DPM versus 44,456 +/- 14,486 DPM +/- SD (p less than 0.05) and 40,083 +/- 16,350 DPM versus 9100 +/- 4114 DPM (p less than 0.05), respectively]. In control rats, about two-thirds of total lung gallium was located in the interstitium, whereas in CFA-treated rats it was found in the mononuclear cells of lung granulomas. Gallium tracks were more numerous in the alveolar macrophages (AM) of CFA-treated rats than in control AM (28.4 +/- 10.0/field versus 8.4 +/- 3.8/field, p less than 0.001) but the number of tracks was proportional to the number of AM (52.4 +/- 18.7 versus 12.2 +/- 4.3, respectively; p less than 0.001). It is concluded that in rats with CFA-induced lung granulomatosis 1) pulmonary gallium uptake increases, 2) mononuclear cells are responsible for this uptake in both granulomas and AM, and 3) the increased uptake is due to the increased number of mononuclear cells.

Animals↗

Anti-Ro-positive lupus and hereditary angioneurotic edema. A 7-year follow-up with worsening of lupus under danazol treatment.

A 24-year-old woman, having familial hereditary angioneurotic edema (HAE) treated with danazol, developed an anti-Ro-positive lupus featured by a mild erythematous eruption that seemed initially to decrease and then worsened under danazol, and dramatically improved after danazol was withdrawn. The relationship between lupus and HAE is discussed with special reference to the hormonal sensitivity of autoimmune diseases. It is possible that the responsibility of danazol as well as the immunogenetic background can explain the clinical course of this association.

Adult↗

Acute lesions induced by alpha-irradiation of intestine after plutonium gavage of neonatal rats.

After gavage of two-day-old rats with 238Pu(IV)-citrate at 17.4 MBq/kg (122 kBq per animal), 45 per cent of the animals died during the second week following ingestion. Histological analysis showed that death was due to acute intestinal lesions caused by alpha-radiation that resulted in denudation of the ileum. Under these experimental conditions, the total alpha-dose delivered to the ileal wall and its contents was estimated at 150 Gy. No acute lesions were observed after gavage of two-day-old rats with Pu-citrate at 5.3 MBq/kg.

Acute Disease↗

Effects of the chemical forms and valency states of neptunium on its jejunal transfer in the rat.

The transfer of various Np(IV) and Np(V) chemical forms across the small intestine of rats was measured in instilled and perfused jejunum. Instillation of Np(V) nitrate together with citrate or DTPA resulted in the same absorption of Np as after instillation of Np(V) nitrate alone (3 per cent per hour). Perfusion of Np(V) nitrate with bicarbonate or DTPA resulted in a similar transfer (2 per cent) but added citrate or ascorbate resulted in reduced transfer (0.8 per cent). Addition of phytate reduced Np transfer in both instilled and perfused jejunum (0.4 per cent). Np(IV) transfer was usually the same as, or less than that of, the corresponding Np(V) forms. Np(IV) transfer was similar in perfused and instilled jejunum, increasing from 0.2 per cent in the presence of citrate and phytate, to 1 per cent with EDTA and DTPA. Except for phytate, all the forms of Np(V) tested behaved like Np(V) nitrate after transfer from the intestine or after intravenous injection. By contrast, the behaviour of Np(IV) varied for all the forms tested and, for a given form, varied as a function of the experimental procedure used, i.e. jejunal instillation, perfusion, or intravenous injection. These findings suggest that the intestinal transfer of Np might occur via the intercellular pathway, and that it is controlled by both the molecular weight of the Np compound and its stability constant.

Animals↗

Beryllium metal solubility in the lung, comparison of metal and hot-pressed forms by in vivo and in vitro dissolution bioassays.

The solubility of two industrial forms of beryllium, i.e. particles of metal powder and particles of hot-pressed beryllium, was investigated using in vivo and in vitro models. In the in vivo model, baboons and rats were used and were injected via the trachea with amounts of beryllium equivalent to 100,500 and 1000 fold the maximum permissible concentration (MPC) recommended by the US Occupational Safety and Health Administration. In vivo experiments showed that in both species the daily beryllium solubility rates were about 5 X 10(-6) for metal particles and that in rats the daily beryllium solubility rate was about 5 X 10(-5) for the hot-pressed particles. During the 10 months of the experiment with baboons, urinary excretion of beryllium was proportional to the amount administered. With regard to results for the in vitro models, the outcome of the acellular dissolution test using a serum simulant was not consistent with the in vivo results, though a cellular model using cultured macrophages showed the same trends in the dissolution rates for the two forms of beryllium as those observed in vivo. This result suggest that a cellular rather than an acellular dissolution model would be better a predicting solubility of beryllium compounds in the lungs.

Animals↗

[Effect of in vivo aging on the growth of rat fibroblastic cells from cutaneous explants].

The migration of fibroblastic cells from explants and the fibroblastic proliferation were two important parameters of healing. They were studied from animal explants of different ages and correlated with a qualitative and quantitative histologic analysis of the cutaneous tissue. These results confirm the decrease of the migration-proliferation capacity of the fibroblasts from cutaneous explants with age. This decrease was associated during maturity with a decrease of cell density in the dermis. It was no longer correlated during the passage from the adult to the senescent state. We must therefore admit an evolution in cell differentiation.

Animals↗