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Biomedical subjects

M Roberfroid

Publications and source records attributed to M Roberfroid.

At least 145 records · Page 8Linked to original sources

Mutagenicity tests with styrene oxide in mammals.

The capability of styrene oxide to induce chromosome damage in vivo has been tested in the male mouse by examination of bone-marrow cells, by scoring micronuclei in polychromatic erythrocytes, by observation of meiotic chromosomes from treated males and by the dominant-lethality test. Furthermore, studies have been performed on short-term cultures of human lymphocytes in vitro. Whereas an increase in the yield of chromatid and chromosomal aberrations was observed after exposure in vitro, only negative results were obtained in the tests in vivo. One has, therefore, to conclude that styrene oxide is potentially capable of breaking mammalian chromosomes but that an exposure to an acute dose in vivo does not produce visible damage in somatic cells or in male germ cells.

Animals↗

Mutagenicity of acrylonitrile.

Incubation of Salmonella typhimurium strains in an atmosphere of 0.2% gaseous acrylonitrile increased the numbers of his+ revertants/plate only in the presence of a fortified S9 liver fraction. The mutagenic effect was particularly pronounced with strains TA1530, TA1535 and TA1950 and much weaker with strains TA100, TA98 and TA1978. The results of bacterial fluctuation tests confirmed the necessity of the presence of S9 mix and showed the particular sensitivity of TA1530. The reversion rate varied with the S9 mix composition, the animal species utilized and the type of pretreatments applied to the animals. The mutagenicity of acrylonitrile in S. typhimurium is therefore microsome-mediated and is particularly discernable with strains sensitive to base-substitution mutagens.

Acrylonitrile↗

Specific modification of the properties of the N-hydroxylase. Relationship with carcinogenesis by aromatic amides.

N-hydroxylation represents the first and limiting step in the metabolic pathway leading to the carcinogenic activity of aromatic amines and amides. Using a method recently developed by the same authors (Analytical Biochemistry, in press), the effects of pretreatment of male adult rats with N-2-acetylaminofluorene (2AAF), N-4-acetylaminofluorene (4AAF), N-4-acetyl-aminobiphenyl, (4-AABP), and phenobarbital (PB), on the kinetic parameters of the N-hydroxylase activity have been evaluated and compared. Our resutls clearly demonstrate that both hepatocarcinogenic amides, 2-AAF and 4-AABP very significantly increase the affinity of the activating enzyme towards both substrates; on the other hand, 4-AAF and PB, which are non-carcinogenic compounds slightly decrease the affinity of the enzyme. In conclusion, the carcinogenic aromatic amides seem to specifically modify the catalytic properties of the enzyme responsible for their own metabolic activation.

2-Acetylaminofluorene↗

Gamma glutamyl transferase: application of a new radiochemical assay to the analysis of its subcellular distribution in the rat liver.

gamma-Glutamyl transferase (gamma-GT) is a key catalyst in the metabolism of glutathione. Its activity in the rat liver is usually very low but it increases significantly during the process of chemical hepatocarcinogenesis. A new radiochemical assay is reported which measures the amount of 3H-aniline liberated from gamma-glutamyl-3H-anilide. This assay is highly specific and no biological substances interferes. By applying this new assay to the analysis of the subcellular distribution of the rat liver gamma-GT, it is shown that it distributes between two pools, one which corresponds to a membrane-bound enzyme, the other to a soluble enzyme. The subcellular distribution of gamma-GT is discussed by comparison with the patterns of distribution of classical marker enzymes.

Animals↗

Acute biotoxic effect of styrene on rat liver. Correlation with enzyme-mediated mutagenicity of benzpyrene and acrylonitrile.

Styrene is commonly used in western Europe for the manufacture of plastics suitable for packaging foodstuffs. This report demonstrates that, injected intraperitoneally at a dose as low as 10 mg/kg, styrene modifies the catalytic properties of aryl hydrocarbon hydroxylase by reducing its KM value. A similar effect is reported for two potent chemical carcinogens, 3-methylcholanthrene and benzo(a)pyrene. Ethylbenzene and benzo(e)pyrene and phenobarbital do not produce the same effect. Pretreatments of the rats with chemicals which modify aryl hydrocarbon hydroxylase also increase the capacity of the liver enzymes to activate benzopyrene to a mutagenic intermediate in vitro, as measured by the Ames test for mutagenicity. Exposure to both styrene and the other modifiers of the xenobiotic-metabolizing enzymes could thus influence the carcinogenic and toxic effects of chemicals which are activated by these enzymes. This hypothesis needs further investigation.

Animals↗

Gas chromatographic and mass fragmentographic assays of carcinogenic polycyclic hydrocarbon epoxide hydratase activity.

A specific and very sensitive procedure for the determination of epoxide hydratase activity in hepatic microsomes is described. Any polycyclic hydrocarbon epoxide can be used as a substrate; in this study, benzo(a)anthracene-5,6-oxide, benzo(a)pyrene-4,5-oxide and 3-methylcholanthrene-11,12-oxide were utilized. The corresponding trans-diols formed during incubation are separated and evaluated using either an electron-capture gas chromatographic method for the determination of their chloromethyldimethylsilylated derivatives or gas chromatographic-mass fragmentographic measurement of their trimethylsilylated derivatives. Concentrations as low as 1 ng per millilitre of incubation mixture can be estimated.

Animals↗