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M Mercier

Publications and source records attributed to M Mercier.

At least 109 records · Page 6Linked to original sources
PubMed1982

Role of glutathione in liver-mediated mutagenicity of acrylonitrile.

The mutagenic activity of acrylonitrile (ACN) towards the Salmonella typhimurium strain TA1530 was evaluated after a short preincubation time in liquid medium in the presence of microsomes, cytosolic fractions and post-mitochondrial fractions of liver from untreated and phenobarbitone (PB)-pretreated rats and mice. The effect of the presence of glutathione (GSH) was also examined. GSH enhanced the microsomal-mediated mutagenicity of ACN; that effect was abolished in the presence of CO. The effect of GSH was usually greater after pretreatment by phenobarbitone. Other sulfhydryl compounds induce a weaker mutagenic activity than GSH. These observations support the hypothesis of a mediated formation of a mutagen involving GSH, but the adduct between ACN an GSH was not mutagenic.

Acrylonitrile↗
PubMed1982

Mutagenicity of three aromatic amines in the presence of fractions from various tissues.

The mutagenic activity of 2-aminofluorene, 4-aminobiphenyl and 3,2'-dimethylaminobiphenyl towards Salmonella typhimurium strain TA1538 was tested in the presence of post-mitochondrial fractions of liver, kidney, intestine, colon and testicle from untreated and pretreated rats. The metabolic activation capacity of these various fractions was very different. In the experimental conditions, no relationship was found between the mutagenic activity and the carcinogenicity of the three aromatic amines.

Aminobiphenyl Compounds↗
PubMed1982

In vitro covalent binding of acrylonitrile to rat liver proteins.

The irreversible protein binding of [3-14C]acrylonitrile (ACN) was evaluated in the presence of microsomes, cytosolic and post-mitochondrial fractions of rat liver. Spontaneous binding was measured after incubation of ACN in the presence of the various liver fractions at 4 degrees C and 37 degrees C respectively and in a comparative study performed at 37 degrees C in the presence of S9 or bovine serum albumin (BSA). The effect of various inducers and inhibitors was investigated. A spontaneous binding resulting from a direct alkylation by ACN seemed to play an important role; however, binding resulting from the microsomal activation of ACN into reactive intermediate(s) was also detected.

Acrylonitrile↗
PubMed1981

Mutagenicity of styrene in the Salmonella typhimurium test system.

The mutagenic activity of styrene was investigated by incubating the strains of Salmonella typhimurium in gaseous atmospheres. The sensitive strains were TA1530, TA1535 and TA100. In that method, styrene regularly showed a mutagenic activity in the presence of a fortified liver post-mitochondrial fraction. The mutagenic activity remained weak. Moreover, it seemed that a volatile mutagenic intermediate was formed metabolically during the assays; its identity remains unknown.

Animals↗
PubMed1981

Mutagenicity of n-nitrosodiethanolamine and its acetyl derivatives.

The mutagenicity of N-nitrosodiethanolamine and its mono- and di-acetyl derivatives was tested in the S. typhimurium test system, in cytogenetic studies and in the micronucleus test. N-nitrosodiethanolamine had no mutagenic effects towards several strains of S. typhimurium either in the absence or in the presence of metabolic activating systems. Its diacetyl derivative exerted mutagenic effects towards the S. typhimurium strains TA1530 and TA100. Neither compound increased significantly the nubmer of chromosomal aberrations or of micronuclei in mice.

Animals↗
PubMed1981

Effect of several factors on the liver extract mediated mutagenicity of acrylonitrile and identification of four new in vitro metabolites.

The mutagenicity of acrylonitrile (ACN) was tested with Salmonella typhimurium TA1530 after a preincubation period of the chemical with a rat liver post-mitochondrial fraction in liquid medium. Several pretreatments were applied to the animals before the preparation of the liver fractions and different compounds added to the incubation mixture, which were shown to modify the liver mediated mutagenic activity of ACN. Four metabolites: cyanoacetic acid, cyanoethanol, acetic acid and glycolaldehyde were identified after incubation of ACN with the rat liver homogenate. From both sets of results, an in vitro metabolic scheme is proposed to ACN, which postulates the intermediate formation of a radical species and an epoxide.

Acetaldehyde↗
PubMed1981

Identification of two urinary metabolites of rats treated with acrylonitrile; influence of several inhibitors on the mutagenicity of those urines.

Urines collected from rats injected with acrylonitrile (ACN) were mutagenic towards Salmonella typhimurium TA1530; this activity was reduced when the animals were pretreated by pyrazole (inhibitor of alcohol dehydrogenase) and suppressed after pretreatment either by CoCl2 and SKF 525-A (inhibitors of the mixed-function oxidases system) or by trichloroacetonitrile (radical trapping agent). On the other hand, two urinary metabolites (cyanoethanol and cyanoacetic acid) have been detected by gas chromatography. One possible scheme for the in vivo metabolism of ACN is presented which postulates the intermediate formation of a radical species and of an epoxide.

Acetates↗
PubMed1981

Mutagenicity of acrylonitrile in mouse.

The capacity of acrylonitrile (ACN) to produce chromosome aberrations in mammals was studied in somatic and germ cells of male NMRI mice. Induction of chromosome aberrations was followed in bone marrow cells 6, 18, 24, 48 and 72 h after an i.p. injection of 20 or 30 mg/kg acrylonitrile, and polychromatic erythrocytes were examined for the presence of micronuclei 24, 30 and 48 h after injection. The dominant lethal test served to detect chromosome aberrations in meiotic and postmeiotic male germ cells. All the tests utilized yielded negative results, so that it may be concluded that acute treatment with acrylonitrile has no clastogenic effects on male mouse cells in vivo.

Acrylonitrile↗
PubMed1981

In vivo and in vitro effects of 3-methylcholanthrene on the microsome-mediated in vitro mutagenicity of 2-acetylaminofluorene.

Pretreatment of rat, hamster or mouse by 3-methylcholanthrene (3-MC) largely induces the liver microsomal N-hydroxylase activity. The same pretreatment given simultaneously with 2-acetylaminofluorene (2-AAF) inhibits the hepatocarcinogenicity in the rat but not in the hamster. The present report compared the in vivo and in vitro effects of 3-MC on liver microsomal N-hydroxylation and liver microsome-mediated mutagenicity of 2-AAF in hamster, rat and mouse. The induction of hamster or mouse liver microsomal N-hydroxylase activity correlated well with the increase in the microsome-mediated mutagenicity of 2-AAF. With rat, however, even though the N-hydroxylase activity is largely enhanced, microsome-mediated mutagenicity is significantly reduced after pretreatment with 3-MC. Such a reduction parallels a decrease in enzyme affinity. Added in vitro to the incubation medium, 3-MC (microM concentration) inhibits both the N-hydroxylase activity and the microsome-mediated mutagenicity of 2-AAF. Those data are discussed in relationship with the biological interactions between 3-MC and 2-AAF.

2-Acetylaminofluorene↗
PubMed1981

Preparation and analysis of a lung microsomal fraction from control and 3-methylcholanthrene treated rats.

In order to facilitate the homogenization of lung tissue it was previously incubated with collagenase during 30 minutes. Morphological observations were performed in order to ascertain the cell integrity. The enzymatically digested tissue was homogenized in a 0.25 M sucrose solution containing 1 mM EDTA, 3 mM imidazole (pH.7.3) and supplemented with 1 mM imipramine in order to stabilize the mitochondria, which otherwise might contaminate the microsomal fraction. The homogenate was then centrifuged and subdivided into four fractions which were analyzed for their content in protein and for the activities of so-called marker enzymes. The cytochrome P450 level was measured in both control and 3-methylcholanthrene preparations. The activities and the kinetic parameters of lung benzpyrene hydroxylase and aldrin epoxidase were measured using the lung microsomal fractions from control and previously 3-methylcholanthrene treated rats; 3-methylcholanthrene pretreatment modified the catalytiac properties of both enzymes.

Animals↗
PubMed1981

Metabolic activation and mutagenicity of 4 vinylic monomers (vinyl chloride, styrene, acrylonitrile, butadiene).

The mutagenic activity and the metabolism of four vinylic monomers; vinyl chloride, styrene, acrylonitrile and butadiene are reviewed. Those chemicals are converted by the mixed function oxidases system of the endoplasmic reticulum into reactive intermediates which can interact with macromolecules within the cell. In order to examine the mutagenic activity of these compounds and their metabolites, different mutagenicity testing systems have been used: tests with S. typhimurium, E. coli, Schizosaccharomyces pombe, Saccharomyces cerevisiae, V79 Chinese Hamster cells, CHO cells, Drosophila melanogaster as well as evaluations of chromosome aberrations.

Acrylonitrile↗
PubMed1980

Subcellular fractionation of isolated rat hepatocytes. A comparison with liver homogenate.

An improved method for the homogenization and the subsequent subcellular fractionation of hepatocytes isolated from adult rat liver is described. The homogenization procedure developed in the present study allows the preservation of the integrity of subcellular structures, as demonstrated by measurement of the activities of representative enzymes as well as by determination of their latency. The activities of representative marker enzymes, as calculated on subcellular fractions obtained by differential centrifugation of the homogenate, are identical whether the homogenate arises from isolated hepatocytes or from the whole liver. Moreover, there is a close similitude between the kinetic parameters (Km and V) of two microsomal cytochrome P450-dependent mixed-function oxidases, namely aniline hydroxylase and aminopyrine demethylase determined on microsomal preparations obtained either from isolated cells or from the whole liver.

Animals↗