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G Lespinats

Publications and source records attributed to G Lespinats.

At least 19 recordsLinked to original sources
PubMed1992

Mapping of intracellular halogenous molecules by low and high resolution SIMS microscopy.

The subcellular distribution of halogenous molecules has been studied by SIMS microscopy in cultured cells of a human breast carcinoma (MCF-7 cell line). Two instruments of microanalysis were used. A low lateral resolution ion microscope (SMI 300 CAMECA) and a prototype scanning ion microscope equipped with a cesium gun that gives high lateral resolution images. This apparatus has been developed by G Slodzian, in Onera Laboratories (Office National d'Etudes et de Recherches Aérospatiales). Molecules studied by low lateral resolution ion microscope were halogenous steroids: fluorometholone, triamcinolone, bromocriptine and bromoandrosterone. Analytical images show that the first two compounds are mainly localized in the nuclear structure of MCF-7 cells whereas the last two molecules are localized in cytoplasm of these cells. Images were obtained with a resolution of 1 micron. With the scanning ion microscope, it is now possible to obtain images at the ultrastructural level. Four analytical images can be simultaneously obtained by a single scan of the imaged area, corresponding to a depth of erosion of the section of ten nm. The intranuclear distributions of three pyrimidine analogs, 5-bromo-2'-deoxyuridine, 5-iodo-2'-deoxyuridine and 5-fluorouracil have been studied in phase S and M of MCF-7 cells and these images have been compared to the distribution of sulfur, nitrogen and phosphorus. All these images have been obtained with a lateral resolution better than 100 nm.

Adrenal Cortex Hormones↗
PubMed1990

Intracellular localization of drugs in cultured tumor cells by ion microscopy and image processing.

Several drugs, containing a halogen atom, F or Br, that are being used in antiviral or anticancer therapy, were studied for their localization in cultured cells by ion microanalysis. The association allows to reduce the exposure time to define the intracellular localization of the studied element. The topography of the cells is given by the image of the polyatomic ion 26CN-. The image of the distribution of 81Br- or 19F-, coded in another color scale, can be superimposed, giving a polychromic image of the cell, thus showing the intracellular localization of the compound. MCF-7 tumor cells were cultured in the presence of pyrimidine derivatives. 5-Bromo-2'-deoxyuridine (BUdR) and 5-trifluorothymidine (F3TdR) were localized in the nucleus, 5-fluoro-2'-deoxyuridine (FUdR) in the nucleus and only in some nucleoli. The method is simple and rapid, as compared with techniques using radiolabeled compounds, or with immunocytochemical techniques. It is possible to observe two different compounds in the same cell. It could be applied to other compounds containing a halogen atom.

Bromodeoxyuridine↗
PubMed1988

Cis DDP in combination with selenium and sulfur. Subcellular effect in kidney cells. Electron microprobe study.

Cis DDP is an anticancer agent used in the treatment of diverse cancers, but its use has been limited by its nephrotoxic effect. We sought to modify this major toxic side effect by the addition of S2O3-- (sodium thiosulfate) or SeO2 (selenium dioxide) or both. In the present study, only ultrastructural and X-ray microanalysis data are reported. No kidney lesions were observed after the administration of SeO2 and Cis DDP in contrast to Cis DDP with S2O3-- or with S2O3-- plus selenium. An organelle of the kidney cell, the lysosome, has a particular role in the concentration of mineral elements in this cell. Platinum was observed in the lysosome along with sulfur, after the administration of Cis DDP and S2O3. Platinum, selenium and sulfur were observed after administration of SeO2, S2O3 and Cis DDP. No mineral deposits were observed after administration of SeO2 and Cis DDP. The role of sulfur seems to be very different from that of selenium. We hypothesize that sulfur favors the intralysosomal concentration of platinum or that selenium associates with platinum. The fact that selenium is not reabsorbed by the kidney cell seems to favor the hypothesis of urinary elimination of platinum. The present work confirms our previous study concerning the role of SeO2 in combination with Cis DDP.

Animals↗
PubMed1987

Evidence for serotonin (5HT) binding sites on murine lymphocytes.

The binding of 3H-labeled serotonin (or 5-hydroxytryptamine: 5HT) to mouse lymphocytes was investigated. It was shown to be highly specific, time-dependent, saturable and partly reversible. Saturation analysis demonstrated a Kd of 198 nM and B max of 3.53 nM. We studied receptor specificity by using different types of serotonin antagonists, and numerous other substances. Serotonin was found to be the most effective drug among those tested in inhibiting the binding of 3H-5HT, having an IC50 of 194 nM. The fact that 5HTP, a 5HT precursor, had no inhibitory capacity indicated the high specificity of these 5HT binding sites. Dopamine was somewhat able to competitively inhibit 5HT fixation (IC50 = 27,000 nM), whereas norepinephrine and histamine had no effect. Lastly, we investigated the cellular specificity of this binding, and observed that nonmacrophage peritoneal cells extensively bound serotonin under the same conditions as spleen cells. This is the first direct demonstration of 5-hydroxytryptamine receptors on mouse lymphocytes. The presence of these binding sites can contribute to the understanding of the suppressive effect of 5HT on mouse immunoreactivity.

Animals↗
PubMed1985

In vivo and in vitro anti-tumour activity of dimaprit.

Dimaprit, a histamine H2-receptor agonist, injected daily i.p. to fibrosarcoma-bearing mice, induced a decrease in tumour growth and an increase in survival. Dimaprit, added to tumour cell cultures (10(-4) M), inhibited the incorporation of 3H-thymidine while embryonic cell cultures were unaffected. This particular anti-tumour activity is probably H2-independent as histamine and impromidine have no effect on tumour cell cultures.

Animals↗
PubMed1985

Inverse correlation between tumor incidence and tissue histamine levels in W/WV, WV/+, and +/+ mice.

The influence of mast cells on tumor incidence and growth rate was studied in 2 grafted tumor models (fibrosarcoma MC-B6-1 and the Lewis lung carcinoma 3LL). Three kinds of WBB6F1 mice (a cross between WB/ReJ-W/+ and C57BL/6J-WV/+ mice) were used: W/WV (deeply mast cell depleted), WV/+ (partially mast cell depleted), and +/+ (normal mast cell number). The presumed resistance of F1 hybrids to tumor cells of parental origin was observed in 12 of 13 +/+ mice, but only in 11 of 22 WV/+ mice and in none of 39 W/WV mice. Tumor incidence and metastasis incidence were inversely correlated with tissue histamine levels and mast cell number. Growth rates of tumors were similar in W/WV and WV/+ mice, but the tumor growth rate was much slower in the only +/+ mouse in which the tumor grew. These results confirm the protective role of mast cells against tumors.

Animals↗
PubMed1984

Role of T suppressor cells in the cycling of the immune response against a murine fibrosarcoma.

Antitumor immunity against a fibrosarcoma in C57BL/6 mice was obtained by means of a semi-allogenic somatic hybrid cell derived from the fusion of this C57BL/6 fibrosarcoma (MCB6-1) and A9 cells of C3H origin. In a Winn assay, this immunity could be transferred by T lymphocytes to normal C57BL/6 recipient mice during an early and a late phase after immunization. There appeared to be a transient non-responsive period during which no immunity could be transferred. Injection of cyclophosphamide (CY) into mice before immunization increased the level of immunity during this period, and reconstitution of animals with normal spleen cells abolished the effect of CY. During the non-responsive period, suppressor cells were demonstrated in the spleen: the i.v. transfer of these suppressor cells to normal mice significantly inhibited the induction of antitumor immunity; the suppressive effect was transferred by T lymphocytes of the Lyt-2+ phenotype. No suppressive effect on antitumor protection was observed when suppressor cells were transferred simultaneously with immune T lymphocytes in the Winn assay. From these findings, it appears that T-suppressor cells regulate the antitumor response, interfering with the afferent (induction) arm of the immune response.

Animals↗
PubMed1984

Tissue histamine levels and mast cell numbers in tumour-bearing mice.

In C57BL/6 mice bearing the 3LL carcinoma and in C3H mice bearing the McC3 -1 fibrosarcoma (18th passage), the increase in skin histamine levels was correlated with the increase in mast cell number. The number of cells able to incorporate tritiated thymidine was proportional to the mast cell number. These results strengthen the notion that, in tumour-bearing rodents, the increase in tissue histamine is an active phenomenon.

Animals↗
PubMed1984

Histamine and serotonin suppression of lymphocyte response to phytohemagglutinin and allogeneic cells.

Histamine added to murine spleen cells suppressed in vitro proliferation of lymphocytes induced by PHA or allogeneic spleen cells. Another vasoactive amine, serotonin (5-hydroxytryptamine), exerted a similar inhibitory activity on PHA- or allogeneic cell-induced lymphocyte proliferation. Anti-H2 histamine antagonists, cimetidine, metiamide, and ranitidine, blocked the histamine and serotonin suppressive effect. Cyproheptadine, an anti-H1 histamine and anti-serotonin antagonist, and methysergide, an anti-serotonin antagonist, also blocked histamine and serotonin inhibitory activities. These data suggest the presence, on lymphocytes, of receptors for serotonin which might be related to histamine receptors.

Animals↗
PubMed1984

Suppressor T cells in BCG-treated mice interfere with an in vivo specific antitumoral immune response.

The interference by BCG in the induction and expression of a specific antitumoral immune reaction was studied in B6 mice, using the in vivo Winn assay and also active immunization. T cells immunized against MCA-induced fibrosarcoma (MC B6-1) transferred together with the tumour cells protected the syngeneic host against tumour take. Pretreatment of normal B6 mice with moderate or high doses of BCG prevented the development of a protective immune response after immunization. Moreover, a single dose of 1 mg, or 2 doses of 0.01 mg BCG, completely eliminated an established antitumour immunity. Suppressor cells are involved in the BCG-induced inhibitory effect; they interfered (1) with the expression of the antitumour response, since their addition to immune T cells in the Winn test resulted in decreased protection and (2) with the induction of the antitumour response, since injection of spleen cells from BCG-treated mice (BCG SpC) into normal mice before immunization inhibited the development of immunity. Treatment of BCG SpC with anti Thy 1.2 and anti Lyt 1.2 antibodies plus complement before injection into normal mice significantly decreased the suppressive activity, showing that the suppressor cells induced by BCG are T cells expressing the Lyt 1+ phenotype. The partial increase in protection obtained after IL-2 administration to BCG-treated mice suggests that the suppressive action of BCG SpC on the IL-2 producing capacity of helper T cells is only one of a number of possible mechanisms of T-cell-mediated suppression.

Animals↗
PubMed1984

Effect of selenium in combination with cis-diamminedichloroplatinum(II) in the treatment of murine fibrosarcoma.

cis-Diamminedichloroplatinum(II) (cis-DDP) is a well-known anticancer agent the use of which is limited by its toxicity. Since it has been demonstrated that selenium is able to combine with metals like cadmium and mercury and to reduce their toxicity, we decided to investigate whether it could reduce the toxicity of platinum. We treated fibrosarcoma-bearing mice with a combination of cis-DDP and selenium. The dose of 2 or 4 micrograms selenium/g animal weight had no effect on tumor growth. The i.p. injection of 16 micrograms cis-DDP/g led to early death of animals. The i.p. treatment of tumor-bearing animals with 2 or 4 micrograms of selenium reduced the early mortality induced by cis-DDP at a dose of 16 micrograms/g. Therefore, the addition of selenium allowed the administration of high doses of cis-DDP, which resulted in an improved antitumor effect. Clonogenic assays following drug exposure showed that selenium had no direct effect on tumor cells and did not modify the antitumor activity of cis-DDP. Electron microscopy showed reduced changes in renal cells when selenium was added to the cis-DDP treatment. Microanalysis showed no accumulation of either selenium or platinum within renal cells. These results suggest that the addition of selenium decreases the nephrotoxicity of cis-DDP.

Animals↗
PubMed1984

Stimulation of one particular subset of natural killer cells by peptidoglycans extracted from gram-positive bacteria.

Peritoneal nonspecific cytotoxicity was stimulated by ip injection into C57BL/6 or (C57BL/6 X C3H/He)F1 mice of Staphylococcus aureus peptidoglycan (PGS), which possessed an antitumor effect, and of Micrococcus lysodeikticus peptidoglycan (PGM), which was ineffective against tumors. The natural killer (NK) cell populations elicited by both peptidoglycans had the same phenotype: Thy 1.2+, T200+, Ly 5.1+, Qa5+, and Ly 2.2-. In vivo treatment with sheep anti-mouse beta interferon serum abrogated this effect. The fluids from phorbol myristate acetate-stimulated murine EL 4 thymoma cells enhanced this particular NK activity, and thus PGM-induced effector cells became able to kill solid tumor cells. In conclusion, both PGS and PGM elicited the same particular subset of NK cell populations, and the peptidoglycan structure can play an important role in the intensity of this response.

Animals↗
PubMed1983

Selective increased tissue histamine levels in tumour-bearing rodents.

Histamine levels increased in the fundus of mice bearing a primary 3-methylcholanthrene-induced fibrosarcoma, and in the ventral skin, skeletal muscle and rumen of rats bearing a D.M.B.A. induced mammary adenocarcinoma; they did not increase in the tissues of mice bearing a McC3-1 fibrosarcoma (38th passage) or a Lewis lung carcinoma before the appearance of metastasis, but an increase in histamine levels was observed in dorsal skin, ventral skin and fundus, after the appearance of metastasis.

Animals↗
PubMed1983

Variable susceptibility to NK activity of cloned cell lines derived from a primary rat rhabdomyosarcoma: relationship to metastatic potential.

In vitro cloned lines derived from a primary nickel-induced rat rhabdomyosarcoma exhibited diverse levels of susceptibility to spontaneous NK activity. The presence of NK target structures was revealed by competition assays on all cloned cell lines, and the NK susceptibility of the tumour lines varied according to their osmotic fragility. Tumour cell lines derived from metastatic lung nodules presented similar NK susceptibilities to cells originating from the primary tumour. However, cloned cell lines differed in their capacity to form lung colonies after i.v. injection, and in their potential for invading lungs after s.c. primary tumour development. No correlation was found between lung colonization potential and NK resistance. Studies of the correlation between metastatic potential and NK sensitivity revealed that (1) all the NK resistant tumour cells were highly metastatic; (2) NK susceptible tumour cells could be either highly or weakly metastatic. Therefore, highly metastatic tumour cells could be either resistant or susceptible to NK lysis. We conclude that the property of resistance to NK contributes to a high metastatic potential. However, other properties could counterbalance and finally prevail over NK susceptibility thus enabling NK susceptible cell lines to be also highly metastatic.

Animals↗
PubMed1983

Cytotoxic responses induced by peptidoglycans with or without in vivo antitumor activity.

Cytotoxic responses mediated by effector cells stimulated in vivo were studied after ip injection in mice of peptidoglycans extracted from gram-positive bacteria. A comparison was done between Staphylococcus aureus peptidoglycan (PGS), which possessed an antitumor effect, and Micrococcus lysodeikticus peptidoglycan, which was ineffective against tumors. Both peptidoglycans induced similar effects on the modulation of T-cell cytotoxic response. Both were able to stimulate splenic and peritoneal nonspecific cytotoxicity against YAC-1 lymphoid tumor cells, but only PGS could induce cytotoxicity and cytostasis against solid tumor target cells.

Animals↗