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J Y Le Talaër

Publications and source records attributed to J Y Le Talaër.

11 recordsLinked to original sources
PubMed2000

Biological properties of 5,11-dimethyl-6H-pyrido[3,2-b]carbazoles: a new class of potent antitumour drugs.

Thirteen 5,11-dimethyl-6H-pyrido[3,2-b]carbazoles, structurally related to the antitumour drug ellipticine, were tested for their cytotoxicity against the L1210 murine leukaemia cell line and their antitumour activity against both leukaemias and solid tumours. Most of them showed an interesting antitumour activity against L1210 leukaemia, 4-hydroxy-9-chloro-2,3, 5,11-tetramethyl-6H-pyrido[3,2-b]carbazole displaying a high antitumour activity against L1210 and P388 leukaemias, B16 melanoma and M5076 sarcoma. Despite promising cytotoxic activity, 4-ethoxy-5,11-dimethyl-6H-pyrido-[3,2-b]carbazole had no antitumour activity. The ability of four drugs to induce strand breaks in DNA was studied using the single cell gel electrophoresis assay (comet assay). Most of the molecules induced DNA breaks that were totally or partially repaired after 1 h. The effects of these compounds on the L1210 cell cycle were tested as well as their abilities to induce apoptosis in these cells. Three of them induced a G2/M blockade, without any obvious evidence of apoptosis. The other compound, 4-ethoxy-5,11-dimethyl-6H-pyrido[3,2b]carbazole, did not lead to phase-specific blockade, but was a strong inductor of apoptosis in L1210 cells.

Animals↗
PubMed1997

Mutagenicity of nitro- and amino-substituted carbazoles in Salmonella typhimurium. III. Methylated derivatives of 9H-carbazole.

The mutagenic potency of nine methylnitrocarbazoles, four methylaminocarbazoles and the methylcarbazole parent compounds was evaluated in Salmonella typhimurium TA98 and TA100, in the absence and presence of S9 isolated from Aroclor-induced rat liver. Nitro derivatives were additionally tested in TA98NR and TA98/1,8DNP6, and mutagenicity of nitrocarbazoles bearing methyl groups in positions 1 and 4 was also determined in TA1537 and TA1977, with and without S9. The addition of methyl groups on non-mutagenic carbazole can induce a mutagenic response where the intensity and nature of the effect depends on the position of the substitution: base-pair substitutions were only observed for N-methylated carbazoles, whereas 1,4-dimethylated compounds exhibited frameshift mutagenicity. All these activities depended on the presence of S9. From its dependence on classical nitroreductases, direct mutagenicity of methylnitro derivatives should be attributed to bacterial reduction of nitro groups. The influence of the methyl groups (and other additional substituents) on mutagenicity of these derivatives is discussed through their effects on life-time and reactivity of the intermediates (i.e., hydroxylamines and nitrenium ions), taking into account the nature, the position and the number of substituted sites Mutagenic activity of methylnitrocarbazoles was also tentatively correlated with various molecular descriptors. Among them hydrophobicity was found to be strongly correlated with the mutagenicity of the 1,4diMe3NC isomers. On the other hand, mutagenic potency of the nitrated and aminated methylcarbazoles varied independently of parameters linked to their oxidoreduction properties (i.e., reduction and oxidation potentials, LUMO and HOMO energies).

Amines↗
PubMed1997

Potentiation of cisplatin and carboplatin cytotoxicity by amphotericin B in different human ovarian carcinoma and malignant peritoneal mesothelioma cells.

An in vitro study of the combined cytotoxicity of either cisplatin (CDDP) or carboplatin and amphotericin B (AmB) was undertaken on a set of different ovarian carcinoma (IGROVI, IGROVI-C10, OAW42) and peritoneal malignant mesothelioma (CFB-CARP1) cell lines and ascitic cells freshly obtained from ovarian cancer patients so as to investigate the possibility of overcoming their resistance to platinum compounds. Growth-inhibition curves obtained 6 days after a 2-h period of exposure to the drugs showed that AmB at 5-10 mg/l allowed a 5- to 10-fold decrease in the 50% growth-inhibitory concentrations (IC50) of CDDP and carboplatin on either sensitive or resistant cells. Intracellular platinum assays with IGROVI cells showed that AmB acted by increasing dramatically the platinum uptake at a proportion that accounted for the increase in cytotoxicity. In the subline IGROVI-C10, a 10-fold resistant subline of IGROVI, AmB at 10 mg/l allowed recovery to the level of sensitivity seen in the parental cell line in the absence of AmB but not to the level observed in the presence of AmB. Acquisition of resistance mechanisms that are independent of the regulation of platinum uptake might be involved in this cell line. Thus, AmB might act by increasing the intracellular concentration of platinum without modifying the resistance mechanism involved downstream. However, in our models an increase in the intracellular level of platinum was always sufficient for the recovery of chemosensitivity in vitro. We also show that the phosphodiesterase inhibiting methylxanthines act synergistically with AmB. The latter drugs are weakly toxic and could also attenuate the nephrotoxicity of AmB.

Adenocarcinoma↗
PubMed1994

Biological markers and ovarian carcinomas: galactosyltransferase, CA 125, isoenzymes of amylase and alkaline phosphatase.

We present a comparative study of several biological markers (galactosyltransferase, CA 125, isoenzymes of amylase and alkaline phosphatase) with a view to ovarian carcinoma follow-up. Serum samples were obtained from a population of 75 patients under clinical observation. After a minimum 18-months period, we assessed the prognostic value of the markers. No marker permits the detection of discrete, evolving carcinomas. CA 125 is the marker that gives the best results, particularly in terms of sensitivity. Galactosyltransferase has a lower sensitivity except in the case of endometrioid carcinomas. Simultaneous analysis with CA 125 and galactosyltransferase results in no decisive improvement, other than greater precision in unfavourable prognoses. Isoenzymes of amylase and alkaline phosphatase are of no interest in the follow-up of such carcinomas.

Alkaline Phosphatase↗
PubMed1993

Mutagenicity of nitro- and amino-substituted carbazoles in Salmonella typhimurium. I. Monosubstituted derivatives of 9H-carbazole.

Mononitro, monoamino and monoacetamido carbazoles were assayed for mutagenicity in Salmonella typhimurium strains TA1535, TA1538, TA1537, TA1977, TA98 and TA100, with and without the addition of S9 from phenobarbital-induced rat liver. The role of bacterial metabolism of the nitro group was also studied using the additional strains TA98NR and TA98/1,8DNP6. None of the compounds was active in TA1535, while only 2-nitrocarbazole and 3-nitrocarbazole presented a weak mutagenicity towards its pKM101 derivative, TA100. All four nitrocarbazole isomers were mutagenic for TA1538 and TA98, their activities decreasing in the order: 2-nitrocarbazole approximately 3-nitrocarbazole > 1-nitrocarbazole > 4-nitrocarbazole. Direct-acting mutagenicities for TA1537 were lower than for TA1538, but varied in the same order. Nitro reduction was an important step of metabolic activation of nitrocarbazoles, as indicated by the dramatic reduction of activity with TA98NR, as compared to TA98. Results obtained with TA98/1,8DNP6 showed that O-acetyltransferase was only partly required for the expression of mutagenic potency of these compounds. 2-Aminocarbazole was a weak direct-acting mutagen for TA1538 and TA98. Its activity was strongly increased in the presence of S9 mix, while 3-aminocarbazole became active in these conditions. The acetamido derivatives were consistently less mutagenic than their parent amines. These results show that nitrocarbazoles and aminocarbazoles behave as reactive frameshift mutagens, acting mainly through the formation of esterified hydroxylamines. The very low activity of 4-nitrocarbazole might be related to an orientation of the nitro group perpendicular to the aromatic ring.

Amines↗
PubMed1990

A simple serum galactosyltransferase assay method suitable for routine use.

UDP-Galactose: N-acetylglucosaminyl glycoprotein beta 1-4 galactosyltransferase (GT) catalyzes the transfer of galactose to N-acetylglucosamine from UDP-[3H]Gal. The uncharged reaction product (tritiated N-acetyllactosamine) is separated from the unreacted UDP-[3H]Gal by ion-exchange chromatography. The major advantage of this method is its rapidity compared to other isotopic techniques.

Chromatography, Ion Exchange↗
PubMed1988

Serum galactosyltransferase activity with three acceptors in ovarian cancer patients.

Several laboratories have demonstrated the usefulness of serum galactosyltransferase as a biological marker for ovarian neoplasms. However, contradictory results have been published recently, which might be partially explained by differences in methodology. We thus decided to measure serum galactosyltransferase activity in patients with ovarian cancer and benign gynecological diseases using three different assay systems. A very good correlation was obtained between the results of these assays. Furthermore, we confirm that serum GT is frequently elevated in cancer patients, and is of potential value for their follow-up.

Acetylglucosamine↗
PubMed1985

[Separation of isoenzymatic forms of human serum galactosyltransferase by chromatofocusing and isoelectric focusing. Application to cancerology].

Chromatofocusing is used to separate the multiple isoenzyme forms of human serum galactosyltransferase. At least 11 major peaks of activity are observed in normal sera, which are eluted between pH 4.3 and 6.9; a fraction of activity is eluted above pH 7.0. The normal patterns are compared with those obtained with sera from cancer patients and with an ascitic fluid. Chromatofocusing appears as resolutive as agarose isoelectric focusing.

Ascites↗
PubMed1985

[Determination of human serum galactosyltransferase using a kinetic spectrophotometric technic].

A kinetic spectrophotometric method in which galactose transfer is coupled to the production of NADH, has been adapted to the assay of galactosyltransferase activity in human serum. Under the described conditions, the rate of NADH production is linear with regard to enzyme concentration, and directly depends upon the various biochemical factors which control galactosyltransferase activity.

Acetylglucosamine↗