Congenital deafness. Not a disability.
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Adaptation, Psychological↗
Biomedical subjects
F Poncelet
Publications and source records attributed to F Poncelet.
Cloning and expression of a Clostridium acetobutylicum alpha-amylase gene in Escherichia coli.
A gene library of Clostridium acetobutylicum ATCC824 was constructed in the plasmid vector pEcoR251. The library was tested for the presence of starch hydrolyzing clones. One clone in which the recombinant plasmid, pVP101, conferred alpha-amylase activity to the Escherichia coli host cell, was detected. The gene is carried on a 3.45-kbp BglII restriction fragment. A detailed physical map of pVP101 is presented.
Chromosome Mapping↗
Liver, kidney and small-intestine microsomal-mediated mutagenicity of carcinogenic aromatic amines.
The mutagenicity of 2-aminofluorene, 4-aminobiphenyl and 3,2'-dimethylaminobiphenyl towards Salmonella typhimurium was studied in the presence of microsomes from liver, kidney and small intestine of untreated and pretreated rats. The aim was to study a possible correlation between the organotropism of these amines and their activation into mutagenic intermediates by these three tissues. Pretreatment of the rats with phenobarbital, Aroclor 1254 and 3-methylcholanthrene injected intraperitoneally increased the liver microsomal-mediated mutagenic activity of the three amines but remained without effect on the activating capacity of microsomes from the kidney and small intestine. However, pretreatment with 3-methylcholanthrene administered intragastrically increased the small-intestine microsomal-mediated mutagenicity of 2-aminofluorene almost 3-fold but remained without effect on the mutagenicity of 4-aminobiphenyl and 3,2'-dimethylaminobiphenyl. No mutagenic effect was observed with 4-aminobiphenyl in the presence of kidney microsomes or with 4-aminobiphenyl and 3,2'-dimethylaminobiphenyl in the presence of small-intestine microsomes, obtained from either untreated or pretreated animals. It is concluded that no relationship exists between the mutagenic activities of the three amines, as detected in the Ames test, and their carcinogenic organotropisms.
Aminobiphenyl Compounds↗
Mutagenicity of several derivatives of dipyrido[1,2-a:2',3'-d]imidazoles.
Different derivatives of dipyrido[1,2-a:2',3'-d]imidazoles have been investigated, as mutagens for Salmonella typhimurium. The nature of different substitution groups and their positions on the base ring influenced markedly the mutagenicity of these compounds. From this structure/effect relationship study, it was demonstrated that the 2 and 3 positions were of special interest. The 3-N-hydroxylated compound was the most active mutagen tested. We also observed that the frequently found frameshift mutagens were responsible for base-pair substitution. Metabolic activation by liver S9 mix increased the reversion rates of the strains tested. The SCE assays correlated poorly with the Salmonella/microsome mutagenicity test.
Cells, Cultured↗
Quantitative correlation between the metabolism and the mutagenic activity of N-nitrosopyrrolidine.
The metabolism of N-nitrosopyrrolidine (NPyrr) via alpha-hydroxylation is modified by pretreatments of the animals with compounds which affect the microsomal level of cytochrome P-450 and by addition, in vitro, of 2-diethylaminoethyl-2,2-diphenyl valerate hydrochloride (SKF 525-A), an inhibitor of cytochrome P-450. This phenomenon is due exclusively to the induction or the inhibition of the enzymatic activity involved in the microsomal metabolism. After preincubation in liquid medium, the mutagenic activity of NPyrr towards the Salmonella typhimurium strain TA 1530 is similarly modified by these effectors. A similar effect is not observed when using the plate incorporation method. The mutagenic intermediate is formed by the microsomal fraction. The presence of the S. typhimurium strain TA 1530 decrease the transformation of NPyrr into its ultimate metabolite (1,4-butanediol); there is a relationship between the formation of 1,4-butanediol and the mutagenic activity of NPyrr. The S. typhimurium strain TA 1530 is able to partially transform 4-hydroxybutanal, the first identifiable microsomal metabolite of NPyrr, into its ultimate metabolite (1,4-butanediol).
Animals↗
In vitro and in vivo studies on the potential mutagenicity of alclofenac, dihydroxyalclofenac and alclofenac epoxide.
Alclofenac (A) and two of its metabolites, dihydroxyalclofenac (DHA) and alclofenac epoxide (AE), were tested for their mutagenic potential. Alclofenac and DHA showed no mutagenic, transforming or clastogenic potential in any in vitro experiment. The addition of a supplementary metabolic activation system did not change the response of those two compounds in any test procedures in vitro. AE, an intermediary metabolite between A and DHA, was mutagenic by itself in the Ames test, but in the presence of a liver post-mitochondrial fraction its activity of Salmonella typhimurium was greatly decreased. Dominant lethal mutations were not induced in male rats given alclofenac, and AE had no effect in the micronucleus test. In human volunteers given alclofenac at therapeutic dose levels, no mutagenic activity was found in the urine and no significant increase in the incidence of structural chromosome aberrations was observed in peripheral blood lymphocytes.
Animals↗
Non-mutagenicity of 2-methyl-2,3-epoxybutane and factors influencing the mutagenicity of 2,3-epoxybutane.
The compound 2,3-epoxybutane (2,3-EB) is a direct mutagen for the base-pair-substitution-sensitive strains TA 1530, TA 1535 and TA 100, in the absence and in the presence of metabolic activation by liver S9-mix. Under the same experimental conditions, the 2-methyl derivative of 2,3-EB was not mutagenic, up to 10 mg per plate. The parent compound (2,3-EB) was more active on strain TA 1530 in the presence of liver S9-mix. This was observed at every epoxide concentration tested. The increase of mutagenicity depended on the S9 concentration, the mix composition and to a small extent on the method utilized.
Animals↗
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↗
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↗
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↗
Vinyl chloride and acrylonitrile: activation mechanism and mutagenicity.
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Acrylonitrile↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗