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.

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.

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.

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.

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.

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.

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.

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.