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R Masse

Publications and source records attributed to R Masse.

At least 19 recordsLinked to original sources
PubMed1992

Studies on anabolic steroids--11. 18-hydroxylated metabolites of mesterolone, methenolone and stenbolone: new steroids isolated from human urine.

New metabolites of mesterolone, methenolone and stenbolone bearing a C18 hydroxyl group were isolated from the steroid glucuronide fraction of urine specimens collected after administration of single 50 mg doses of these steroids to human subjects. Mesterolone gave rise to four metabolites which were identified by gas chromatography/mass spectrometry as 18-hydroxy-1 alpha-methyl-5 alpha-androstan-3,17-dione 1, 3 alpha,18-dihydroxy-1 alpha-methyl-5 alpha-androstan-17-one 2, 3 beta,18-dihydroxy-1-alpha-methyl-5 alpha-androstan-17-one 3 and 3 alpha,6 xi,18-trihydroxy-1 alpha-methyl-5 alpha-androstan-17-one 4. These data suggest that mesterolone itself was not hydroxylated at C18, but rather 1 alpha-methyl-5 alpha-androstan-3,17-dione, an intermediate metabolite which results from oxidation of mesterolone 17-hydroxyl group. In addition to hydroxylation at C18, reduction of the 3-keto group and further hydroxylation at C6 were other reactions that led to the formation of these metabolites. It is of interest to note that in the case of both methenolone and stenbolone, only one 18-hydroxylated urinary metabolite namely 18-hydroxy-1-methyl-5 alpha-androst-1-ene-3,17-dione 5 and 18-hydroxy-1-methyl-5 alpha-androst-1-ene-3,17-dione 6 were both detected in post-administration urine specimens. These data indicate that the presence of a methyl group at the C1 or C2 positions in the steroids studied is a structural feature that seems to favor interaction of hepatic 18-hydroxylases with these steroids. These data provide further evidence that 18-hydroxylation of endogenous steroids can also occur in extra-adrenal sites in man.

Androstenols↗
PubMed1992

In vitro dissolution of uranium oxide by baboon alveolar macrophages.

In vitro cellular dissolution tests for insoluble forms of uranium oxide are technically difficult with conventional methodology using adherent alveolar macrophages. The limited number of cells per flask and the slow dissolution rate in a large volume of nutritive medium are obvious restricting factors. Macrophages in suspension cannot be substituted because they represent different and poorly reproducible functional subtypes with regard to activation and enzyme secretion. Preliminary results on the dissolution of uranium oxide using immobilized alveolar macrophages are promising because large numbers of highly functional macrophages can be cultured in a limited volume. Cells were obtained by bronchoalveolar lavages performed on baboons (Papio papio) and then immobilized after the phagocytosis of uranium octoxide (U3O8) particles in alginate beads linked with Ca2+. The dissolution rate expressed as percentage of initial uranium content in cells was 0.039 +/- 0.016%/day for particles with a count median geometric diameter of 3.84 microns(sigma g = 1.84). A 2-fold increase in the dissolution rate was observed when the same number of particles was immobilized without macrophages. These results, obtained in vitro, suggest that the U3O8 preparation investigated should be assigned to inhalation class Y as recommended by the International Commission on Radiological Protection. Future experiments are intended to clarify this preliminary work and to examine the dissolution characteristics of other particles such as uranium dioxide. It is recommended that the dissolution rate should be measured over an interval of 3 weeks, which is compatible with the survival time of immobilized cells in culture and may reveal transformation states occurring with aging of the particles.

Animals↗
PubMed1992

Overview of pulmonary alveolar macrophage renewal in normal rats and during different pathological processes.

We report experimental results on pulmonary alveolar macrophage (PAM) renewal in healthy rats and in rats treated with particles introduced in the lungs. Morphometric studies showed that the lungs of normal rats of the strain used in our study contain 20 x 10(6) PAM, 50 x 10(6) monocytes in alveolar capillaries, and about 3 x 10(5) interstitial macrophages. Pulse labeling with a tritiated thymidine (3HT) gave a labeling index of 0.4% for the monocytes, of which a few could be observed in mitosis within alveolar capillaries. These monocytes are likely to be the PAM precursors. The daily input (greater than 4%) by PAM proliferation exceeds PAM loss by migration to the upper respiratory tract (2.5%). The life span of PAM was measured by sequential counting of lavaged cells after labeling with [125I]iododeoxyuridine instilled intratracheally. The pulmonary lavage procedure used allowed us to recover at least 80% of the whole PAM population. A daily loss of PAM of 8-9% was measured, of which loss by death in the endoalveolar compartment was estimated at 5-6%. During the pathological processes studied, several parameters of PAM renewal were shown to be modified. PAM migration to the upper respiratory tract was frequently inhibited, PAM cytotoxicity was observed, and PAM proliferation increased in some cases and decreased in others. Under most of the pathological conditions investigated, the renewal of endoalveolar macrophages appeared quite different from that in normal rats, and direct blood monocyte migration to the endoalveolar compartment became a major component of PAM renewal.

Administration, Inhalation↗
PubMed1992

[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.m-3). The incidence of lung cancer is not increased and is equal to that of controls when the same cumulated dose is protracted over 18 months at 2 WL (0.042 mJ.m-3).

Administration, Inhalation↗
PubMed1992

Validity and limitations of animal experiments in assessing lung carcinogenicity of cadmium.

Several cadmium compounds have been observed to induce in rats, but in rats only, a dose-dependent increase in lung cancer. A similar sensitivity to lung cancer induction in both humans and rats can be deduced from a comparison of the histogenesis of tumours and the dose response to radiation, since similar numbers of DNA lesions are produced. Since the carcinogenic action of cadmium is limited to the site of deposition, the toxicokinetics of inhaled particles in human and rodents are discussed in relation to the exposure of the respective target cells in both species. It is stressed that the rat may be much more sensitive to the induction of cancer following the retention of poorly soluble compounds. A comparison of the possible dose-effect response in humans and the dose response in rats showed that the shape of the "dose" response cannot be extrapolated. Finally, clonogenicity and DNA repair of tracheal cells sublethally exposed in vitro to cadmium differ significantly in rats and hamsters. This may explain why hamsters exposed in vivo do not develop tumours.

Animals↗
PubMed1991

[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. The higher incidence of tumours observed in the foetal group was mainly due to the high sensitivities of central nervous system and gonads during organogenesis.

Adrenal Gland Neoplasms↗
PubMed1991

Use of unstable chromosome aberrations for biological dosimetry after the first postirradiation mitosis.

The loss of unstable chromosome aberrations after the first postirradiation mitosis makes their use difficult in radiation dosimetry. We describe here a method which, in a cell population observed at this stage, allows retrospective estimation of the frequencies of the unstable aberrations induced at the time of irradiation, and their use as a dosimeter. The laws controlling the behavior of unstable aberrations during mitosis were defined from a large-scale experiment on irradiated human lymphocytes. For cells undergoing the first, second, or third mitosis after irradiation, relationships were determined between the frequency, at irradiation time, of acentric fragments not arising from formation of dicentrics or rings, and the ratio of dicentrics and centric rings appearing without acentric fragments to the total number of dicentrics plus rings. On the basis of this ratio, the method described here provides an assessment of the postirradiation mitotic activity in a cell population. This assessment permitted estimation of the cell distribution and frequency of dicentrics plus centric rings, and of the frequency of acentric fragments at the time of irradiation. The use of this method for retrospective dosimetry after whole-body irradiation under various conditions of exposure is illustrated.

Animals↗
PubMed1990

In vitro therapeutic targeting of neuroblastomas using 125I-labelled meta-iodobenzylguanidine.

The use of labelled radiopharmaceuticals such as metaiodobenzylguanidine (m-IBG) enables neuroblastomas and other malignant cells from neural crests to be visualized. In vitro study of cellular incorporation into human neuroblastoma lines (SK-N-SH, SK-N-MC, LAN I) showed that only the SK-N-SH line retained iodine-125 m-IBG (125I-m-IBG) significantly. Fifty-five percent of the initial activity was retained after 1 hr incubation at a concentration of 10(-7) M of m-IBG (specific activity: 1,480 MBq/mg). Beyond this value, m-IBG uptake mechanisms were saturated. Study of release kinetics showed a rapid first phase (50% released after 4 hr) and a slower second phase (30% of the value retained at the equilibrium point was present after 48 hr), indicating the existence of a storage compartment. Autoradiography studies confirmed the intracytoplasmic localization of m-IBG and showed that a low percentage (3 to 5%) of SK-N-SH cells strongly retained m-IBG. Cytotoxicity tests showed that SK-N-SH cell growth was significantly reduced during the first days of culture, following 2 hr incubation with 1,500 KBq of 125I-m-IBG, whereas no toxic effect on SK-N-MC cells was found at the same activity. Moreover, the toxic effect observed in the SK-N-SH line was clearly related to the use of 125I-m-IBG since the same activity of 1,500 KBq of non-coupled 125I was without effect. For the latter line, colony-forming capacity was reduced for activities of 150 and 1,500 KBq of 125I-m-IBG, with respectively 32% and 38% lower survival rates. The cytotoxic effect of labelled m-IBG was, however, limited in non-saturating concentrations because the specific activity used was too low. Moreover, the low number of cells reconcentrating m-IBG is indicative of the heterogeneous cellular composition of the SK-N-SH line.

3-Iodobenzylguanidine↗
PubMed1990

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↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗