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Biomedical subjects

M Roberfroid

Publications and source records attributed to M Roberfroid.

At least 127 records · Page 7Linked to original sources
PubMed1980

Induction, activation, and inhibition of hamster and rat liver microsomal arylamide and arylamine N-hydroxylase.

By applying a new and highly sensitive assay for measuring N-hydroxy metabolites, the biochemical properties of the microsomal N-hydroxylase from control and 3-methylcholanthrene-treated rat and hamster liver have been analyzed, and the following conclusions have been drawn. (a) Due to a difference in enzyme affinity, the metabolic activation of acetylaminofluorene is more pronounced than that of aminofluorene, a fact which correlates with the difference in the carcinogenic potency of the two compounds. (b) Arylamine N-hydroxylase differs qualitatively as well as quantitatively from arylamide N- hydroxylase mainly in terms of sensitivity to various in vitro inhibitors. (c) 7,8-Benzoflavone and 3-methylcholanthrene are strong inhibitors of liver microsomal N-hydroxylases. This effect could partly explain the inhibition of the hepatic tumorigenicity of acetylaminofluorene in animals simultaneously fed 3-methylcholanthrene. (d) The metabolism of acetylaminofluorene proceeds via both ring- (C-1, C-3, C-5, or C-7) and N-hydroxylation. There is clear reciprocal interaction between these various microsomal pathways. (e) The apparent increase in Km following pretreatment of the rat with 3-methylcholanthrene is due to competitive inhibition of the N-hydroxylase by some of the C-hydroxy metabolites. This effect is not seen in hamster liver.

2-Acetylaminofluorene↗
PubMed1979

Determination of Kováts retention indices with a capillary column and electron-capture detection: application to the assay of the enzymatic conversion of 3,4-epoxy-1-butene into diepoxybutane.

A method is described that allows for alternate operation of a "pin and cup"-type electron-capture detector (ECD) in the normal ECD mode and in the metastable argon ionization mode. By such means, marker n-alkanes can be run without a change of the gas or temperature parameters, and measurements can be made of the Kováts retention indices of unknown compounds that are detectable in trace amounts by ECD only. As an application, tests are reported which support the probable enzymatic conversion of 3,4-epoxy-1-butene into diepoxybutane during incubation of the former with rat liver microsomes.

Animals↗
PubMed1979

Microsomal vinyl oxide synthetase: modification of its kinetic parameters by chemical carcinogens.

The kinetic parameters of liver microsomal vinyl oxide synthetase as well as their modifications under the influence of various pretreatments have been evaluated, using 1,1,2-trichlorethylene (TCE) as a substrate. The results were correlated with those obtained using aldrin oxide synthetase and benzpyrene hydroxylase as typical cytochrome P-450 dependent enzymatic activity. The treatments of animals with chemical carcinogens selectively increase the affinity of those enzymes for their substrates.

Aldrin↗
PubMed1979

Liver extract mediated mutagenicity of acrylonitrile.

The mutagenic activity of acrylonitrile vapours towards Salmonella typhimurium strains strictly depends upon the presence of a liver postmitochondrial fraction. The reversion rate varies according to the animal species from which the S9 fraction is obtained as well as to the pretreatment of the animals. The comparatively weak activating effect of the microsomal fraction and the inability of both SKF525A and carbon monoxide to inhibit the S9 mediated mutagenicity of acrylonitrile (ACN) suggest that the cytochrome P-450-dependent monooxygenases do not play a major role in the metabolic activation of ACN into a mutagenic intermediate (s).

Acrylonitrile↗
PubMed1978

Sensitive gas chromatographic methods for the determination of vinyl epoxide synthetase activity using trichloroethylene as a model substrate.

Two specific and very sensitive methods for the determination of vinyl epoxide synthetase activity in liver microsomes are described. Trichloroethylene, which is used as a substrate, is converted into trichloroethylene oxide by a hepatic epoxide synthetase. Chloral hydrate, the final rearrangement product of trichloroethylene oxide, is determined by electron-capture gas chromatography, either after derivatization with pentafluorophenylhydrazine or after its conversion into chloroform under alkaline conditions. The kinetic parameters of the epoxidation reaction were determined on rat hepatic microsomal suspensions.

Animals↗
PubMed1978

A very sensitive gas chromatographic method for the evaluation of styrene oxidase and styrene oxide hydratase activities.

Styrene is a compound widely used in the manufacture of polystyrenic plastics and it has recently been shown to exert mutagenic effects after metabolic activation into styrene oxide by the microsomal mixed function oxidases; this oxide is further converted into inactive styrene glycol. In order to investigate the relative importance of activation and desactivation processes of styrene, we developed a gas chromatographic method which enables us to simultaneously measure styrene oxide and styrene glycol formed after incubation of styrene with microsomal preparations from different tissues. After selective extraction of the two compounds from the incubation mixture, they are derivatized with pentafluorobenzoyl chloride and measured by gas chromatography using an electron capture detector. The high sensitivity of the method, which allows 0.01 ng of both compounds to be measured, as well as its selectiveity, has permitted us to adequately evaluate the kinetic parameters of styrene oxidase and styrene oxide hydratase activities, as well as their modifications under the influence of various pretreatments of the animals.

Animals↗
PubMed1978

A gas chromatographic method for the evaluation of the vinyl epoxidase activity.

Two alternative specific and very sensitive methods for determination of vinyl epoxide synthetase activity in liver microsomes are described. Trichloroethylene, which is used as a substrate, is converted into trichloroethylene oxide by a hepatic epoxide synthetase. Chloral hydrate, the final rearrangement product of trichloroethylene oxide, is evaluated by electron capture gas chromatography, either after derivatization with pentafluorophenyl-hydrazine or after its conversion into chloroform under alcaline conditions. The kinetic parameters of the epoxidative reaction have been determined on rat hepatic microsomal suspensions.

Animals↗