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M Roberfroid

Publications and source records attributed to M Roberfroid.

At least 37 records · Page 2Linked to original sources
PubMed1988

Inhibition of O2-.- and HO.- mediated processes by a new class of free radical scavengers: the N-acyl dehydroalanines.

N-phenylacetyl dehydroalanines are captodative olefins. They inhibit two processes mediated by superoxide anion (O2-.) in a concentration dependent manner: reduction of NBT to blue formazan and oxidation of epinephrine to adrenochrome. They also inhibit in a dose related way the degradation of deoxyribose produced during either the Fenton reaction or the radiolysis of water, which are the two experimental sources of hydroxyl radical (HO.) production. Based on the results obtained with superoxide dismutase, mannitol, thiourea, and uric acid, we postulate that these competitive inhibitory effects suggest a reaction between the dehydroalanine derivatives and the two oxygen derived radicals. Hydroxyl free radical is scavenged more efficiently than superoxide anion. Substitution of the phenyl ring by methoxy groups does not modify significantly the activity. These molecules possess three target active sites which can react with free radicals.

Alanine↗
PubMed1987

Intestinal carcinogenesis and dietary fibers: the influence of cellulose or Fybogel chronically given after exposure to DMH.

This study was initiated to analyze the effect of a) two characterized vegetal fibers [i.e., a polysaccharide (cellulose) and a mucilaginous substance (Fybogel)], which were b) added at two concentrations (5% and 15% wt/wt), c) as constituents of low (5% wt/wt) and high (20% wt/wt) fat isocaloric diets d) given chronically to rats one week after the administration of 1,2-dimethylhydrazine (DMH); DMH had previously been injected once a week for 15 weeks to induce intestinal carcinogenesis. The dietary consumption, the body weight, and the fecal outflow showed a similar and regular evolution for the rats of all experimental groups; the exception was those receiving the 20% lipids-15% Fybogel diet. That specific diet caused a decrease in body weight concomitant with an increase in dietary consumption and in fecal outflow. The variation in fecal outflow depended on fat and fiber concentrations. The mucilage was more degraded, in absolute and relative amount, than was cellulose when this polysaccharide was included at a 20% lipid diet. Concerning the effect of these two fibers on intestinal carcinogenesis, Fybogel showed an anticarcinogenic property, whereas cellulose did not. The inhibitory activity of Fybogel was on the incidence of intestinal and colonic tumors as well as on the colonic tumor yield. Moreover, it slowed down the rate of colonic formation.

1,2-Dimethylhydrazine↗
PubMed1986

Influence of the nature and the dose of the initiator on the development of premalignant and malignant lesions in rat hepatocarcinogenesis.

Using a triphasic protocol recently described to induce malignant tumors in rat liver, the question has been asked whether both the nature and the dose of the initiator influence the carcinogenic process. Two nitrosamines (diethylnitrosamine DEN and N-nitrosomorpholine NNM) have been used to initiate that process. With regard to the premalignant stages appearing in the liver up to 19 weeks after initiation, there is a dose-dependent relationship between the dose of initiator and both the percentage of the parenchyma occupied by and the number of GGT+ lesions. DEN is always more potent than equivalent doses of NNM. With regard to malignant tumors appearing within the period of observation (up to 44 weeks), the two highest doses (100 and 200 mg/kg) of DEN appear to be the only carcinogenic treatments. Cancer incidence (percentage of rats bearing histologically characterized malignant tumor) is the same after both treatments, but the tumor yield (number of tumors per rat bearing macroscopic tumors) is higher (+/- 2X) after 200 mg/kg than after 100 mg/kg.

Animals↗
PubMed1986

Antimutagenic effects of natural and synthetic hormonal steroids.

Among the steroid molecules, bile acids have been shown to have either a co- or an antimutagenic activity toward various direct and indirect acting mutagens in the Ames test. The present report extends such observations to other steroids having hormonal activity. The main effect of the active hormones is an inhibition of the genotoxicity of both direct and indirect acting mutagens. This effect is strictly structure-related. Moreover, both ethinyl oestradiol and mestranol, which are synthetic derivatives of beta-oestradiol largely used in contraceptive pills, are strong inhibitors of the mutagenicity, acting at nanomolar concentrations. The present article emphasizes the possible role of compounds with steroid structure as modulators of genotoxicity.

Bile Acids and Salts↗
PubMed1986

Comparative analysis of the effect of phenobarbital, dichlorodiphenyltrichloroethane, butylated hydroxytoluene and nafenopin on rat hepatocarcinogenesis.

In order to investigate whether different 'promoters' have the same qualitative and/or quantitative effects on rat hepatocarcinogenesis, 0.05% of phenobarbital (PB), 0.05% of dichlorodiphenyltrichloroethane (DDT), 0.5% butylated hydroxytoluene (BHT) and 0.1% of nafenopin (NAF) were chronically administered in the diet to rats previously submitted to an initiation by diethylnitrosamine and a selection with 2-acetylaminofluorene plus CC14. The animals were killed after 3, 6 and 14 weeks of 'promoters' administration to analyse their effect on premalignant lesions. The quantitative analysis of the gamma-glutamyltransferase positive lesions indicates that as compared to a control group receiving a basal diet after initiation and selection, PB, DDT and BHT enhance the development of these lesions whereas NAF inhibits it. Rats were also killed after 22 weeks of administration to analyse the incidence and the yield of liver cancer. As compared to the control group, PB, DDT and surprisingly NAF enhance the development of liver cancer whereas BHT does not. This suggests that the effect of potential 'promoters' should be analysed on cancer development rather than on premalignant lesions.

Animals↗
PubMed1986

Comparison of the biological effects of phenobarbital and nafenopin on rat hepatocarcinogenesis.

In order to further analyze the biological effects of phenobarbital (PB) and nafenopin (NAF) on rat hepatocarcinogenesis, four experiments were undertaken. In the first one, their "promoting" effect on an ongoing carcinogenic process was analyzed. Rats were initiated by diethylnitrosamine treatment (I) and submitted two weeks later to a selection procedure (S). One week after 2-acetylaminofluorene (2-AAF) release, the animals received for up to 56 weeks a basal diet or a diet containing 0.05% of PB or 0.1% of NAF. The quantitative analysis of the gamma-glutamyl-transferase-positive lesions showed that, 8 to 19 weeks after I, PB enhanced the development of preneoplastic lesions whereas NAF inhibited it as compared to a group receiving a basal diet. However, both compounds enhanced the incidence and the yield of liver cancer starting 27 weeks after I (67% and 95%, respectively, vs 10%). In the second experiment, the effect of chronic administration of PB and NAF given after I without S or after S without I was analyzed. Within a period of observation of 27 to 32 weeks, the incidence of cancer was 10% after I/PB and 75% after I/NAF. No cancer developed after S/PB, S/NAF or NAF alone. The third experiment was designed to test whether NAF had an initiating or selecting effect. The results of the quantitative analysis of the gamma-glutamyl-transferase-positive lesions showed that as compared to diethylnitrosamine, NAF had no initiating effect. When NAF replaced 2-AAF in the selection procedure, few gamma-glutamyl-transferase-positive lesions and no cancer were detected 8 and 32 weeks after I. The fourth experiment indicated that NAF could not prevent the remodeling of preneoplastic lesions induced in the I/S protocol. Even though they both have a "promoting" effect in liver carcinogenesis as evidenced by the increased incidence and yield of cancer, PB and NAF act differently.

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↗