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Biomedical subjects

M Roberfroid

Publications and source records attributed to M Roberfroid.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1987

Promoting effect of oxazepam in rat hepatocarcinogenesis.

In order to check whether the benzodiazepine, oxazepam (OZ), has a modulating effect on the development of liver cancer, it was given to rats previously submitted to two different protocols of hepatocarcinogenesis: the resistant hepatocyte protocol and Pitot's model (initiation-promotion). Its effects were compared with those of phenobarbital (PB) administered under the same conditions. As compared with basal diet, a diet containing 0.05% of PB and 0.1% of OZ enhanced, in both models, the development of gamma-glutamyltransferase-positive lesions in early stages. OZ also had a promoting effect on the development of liver cancers in later stages in both models whereas PB only enhanced it in the resistant hepatocyte protocol. Thus, like PB, OZ may have a promoting effect on liver cancer in rats.

2-Acetylaminofluorene↗
PubMed1987

Dietary modulation of rat liver carcinogenesis.

Rat liver carcinogenesis was induced according to the resistant hepatocyte model of Solt and Farber. One week after the end of the procedure for the rapid growth of altered hepatocytes, one group of rats was submitted to a high fat (20%) regimen up to the end of the experiment. The incidence of histologically confirmed malignant hepatocarcinomas was compared with that observed in a group that remained on a normal diet. The modulating (promoting) effect of the high fat regimen was evident since nine out of 10 animals in this group bore macroscopically detectable tumors and eight out of 10 presented histologically confirmed hepatocellular carcinomas as early as 24 weeks after the beginning of the experiment. At that time, no malignant tumors were detected in the group submitted to the normal fat regimen. These results are similar to those resulting from a porto-caval shunt or the chronic administration of liver tumor promoters. This suggests that at this stage of the carcinogenic process, any treatment inducing chronically metabolic adaptation in a tissue containing preneoplastic nodules modulates positively the progression of these lesions as demonstrated by the dramatic reduction of the lag period for their malignant transformation.

Animals↗
PubMed1987

Potentiation of the therapeutic activity of cyclophosphamide by an original N-acyldehydroalanine.

Research work is currently in progress with the aim of improving the efficacy and/or reducing the toxicity of cancer treatments. The present communication reports on the effect of an original molecule, N-(ortho-methoxyphenylacetyl)dehydroalanine, known as AD20. In a protocol in which L1210 leukaemic cells, AD20 and cyclophosphamide were injected i.p. into BDF1 mice, the association CP-AD20 was more active than CP alone at therapeutic or subtherapeutic doses of CP. If the doses of CP were higher than its optimum therapeutic dose, the association CP-AD20 was more toxic than CP alone. The positive effect of AD20 was also observed when AD20 was given i.v. or when the leukaemic cells were implanted s.c., CP always being injected i.p. Taking into account its low toxicity, AD20 exhibits interesting properties that could support its development as an adjuvant for cancer chemotherapy.

Alanine↗
PubMed1987

Comparison of induction of DNA single-strand breaks and initiation of rat hepatocarcinogenesis by different nitrosamines.

The capacities of nitrosamines to induce DNA single-strand breaks (SSB) and to initiate carcinogenesis in rat liver were compared. N-Nitrosodiethanolamine (NDELA), N-nitrosoethylhydroxyethylamine (NEHEA) and N-nitrosodiethylamine (NDEA) were equipotent in inducing DNA SSB when administered by gavage at doses of 0.35 mmol/kg, 0.015 mmol/kg and 0.37 mmol/kg, respectively. Male Wistar rats were injected with these nitrosamines and were then submitted to a selection procedure. Ten rats per group were sacrificed one week after the end of the selection to see the effects of the nitrosamines on the development of preneoplastic lesions. The numbers of gamma-glutamyl transferase (GGT)-positive lesions per cm2 were 0.8, 2.1, 5.2 and 40.1 in rats treated with saline, NDELA, NEHEA and NDEA, respectively. N-Nitrosobis(2,2,2-trifluorethyl)amine (6F-NDEA), a nongenotoxic and noncarcinogenic nitrosamine, induced 0.7 GGT-positive lesions per cm2. Ten rats per group also received 0.05% phenobarbital in their drinking-water and were killed six months after initiation in order to see the effect of the different nitrosamines on the incidence and yield of tumours. Two extrahepatic cancers were found after administration of NEHEA, whereas two hepatocellular carcinomas were detected after injection of NDEA. No cancer developed in the other groups. Although other factors may influence the process, these results indicate that no simple correlation can be established between induction of SSB in DNA and initiation of tumours by nitrosamines in rat liver.

Animals↗
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

Anti-initiation activity of N-acetylcysteine in experimental colonic carcinogenesis.

N-Acetylcysteine (NAC) is a soluble nucleophile that has been shown to have antimutagenic activity towards various genotoxic agents including 1,2-dimethylhydrazine (DMH). The present report extends such observations by showing the protective effect of NAC against the carcinogenic activity of DMH. This thiol-containing molecule reduced the incidence of rat intestinal tumors. Moreover, it significantly lowered the colic tumor yield as expressed by the number of tumors per rat bearing tumors. With regard to localisation of colic carcinomas, NAC induced a shift from distal to more proximal sites.

1,2-Dimethylhydrazine↗
PubMed1986

Effects of secondary biliary acids on the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine, 2-acetylaminofluorene and 2-nitrofluorene towards Salmonella typhimurium strains.

The two secondary biliary acids (lithocholic and deoxycholic acids) were co-mutagenic when they were each co-incubated with dimethylhydrazine in the presence of Salmonella typhimurium TA 100. These observations were extended to other toxic chemicals, acting as direct (N-methyl-N'nitro-N-nitrosoguanidine and 2-nitrofluorene) or indirect (2-acetylaminofluorene) mutagens. Lithocholic and deoxycholic acids show a similar behavior towards genotoxic molecules. Nevertheless two differences must be noted. Lithocholic acid was the stronger co-mutagen. When lithocholic acid inhibited mutagenic activity of 2-nitrofluorene, deoxycholic acid did not modify it. Interactions between the two secondary bile acids occurred so that the co-mutagenic activity of the mixture of these two bile acids depended on the ratio of their concentrations. Besides their cancer-promoting effect, biliary acids also could have co-initiating effect that could depend upon the ratio of their concentration in the intestine. Calculating the ratio of fecal concentrations of deoxycholic/lithocholic acids thus could be a more sensitive index for cancer risk than simply measuring the fecal concentration of the two biliary acids taken separately.

2-Acetylaminofluorene↗
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↗