PubMed Health⌕ Search

Biomedical subjects

C Malaveille

Publications and source records attributed to C Malaveille.

122 records · Page 7Linked to original sources
PubMed1975

Human, rat and mouse liver-mediated mutagenicity of vinyl chloride in S. typhimurium strains.

Exposure of S. typhimurium strains TA 1530, TA 1535 and G-46 to vinyl chloride increased the number of His+ revertants/plate 16, 12 or 5 times over the spontaneous mutation rate. After 6 h of exposure to vinyl chloride, the mutagenic response for TA 1530 strain was enhanced 7-, 4- or 5-fold when fortified postmitochondrial liver fractions from humans, rats or mice were added. The enzyme-mediated vinyl chloride mutagenicity was dependent on an NADPH generating system and the enzyme activity was localized in a liver microsomal fraction; 9,000 times g liver supernatant was three times more active than microsomes, while liver cytosol or alcohol dehydrogenase did not affect the mutagenicity. Phenobarbitone pretreatment of rats and mice increased the mutagenic response by up to 15-40 percent as compared to untreated controls. The relative mutagenic activities of VCM, taking the value from mouse liver as 100, for TA 1530 strain mediated by 9,000 times g tissue fractions were: rat liver, 80; mouse and rat kidney, 20 and 16; mouse and rat lung, less than 7; human liver (from four biopsy specimens) 170, 64, 70 and 46. Chloroacetaldehyde and chloroacetic acid, a urinary metabolite of VCM, showed toxic effects, while chloroethanol was weakly mutagenic for TA 1530 strain.

Acetaldehyde↗
PubMed1975

In vitro metabolism and microsome-mediated mutagenicity of dialkylnitrosamines in rat, hamster, and mouse tissues.

Rates of conversion of 14C-labeled dimethyl-and diethylnitrosamine by rat and hamster tissue slices to 14CO2 and/or into mutagenic reactants were measured using Salmonella typhimurium G-46 r TA 1530 and fortified tissue fractions in vitro. A correlation between the CO2 production from dimethyl- or diethylnitrosamine in liver or lung and the organ distribution of induced tumors in vivo was observed. As an exception, hamster lung, which is a major target organ in diethylnitrosamine carcinogenesis, did not convert this nitrosamine into metabolites mutagenic for S. typhimurium TA 1530 although the 14CO2 production in vitro was even higher than in hamster liver. The effect of pretreating rats, hamsters, and mice with phenobarbitone on the mutation frequency produced by dimethyl-or diethylnitrosamine in in vitro assays was determined. The relationship between the site of metabolic activation, mutagenicity, and carcinogenicity of the dialkylnitrosamines and the effect of enzyme inducers are discussed.

Animals↗
PubMedDate not supplied

Characterization and identification of 6 mutagens in opium pyrolysates implicated in oesophageal cancer in Iran.

Previous epidemiological studies have indicated an association between the ingestion of opium pyrolysates, dietary deficiencies, and a high incidence of oesophageal cancer in subjects in north-east Iran. Laboratory studies have shown that pyrolysates of opium and particularly of morphine, a major opium alkaloid, are highly mutagenic in bacteria and induce sister-chromatid exchanges in mammalian cells after metabolic activation. We now report the ability of these pyrolysates to transform Syrian hamster embryo cells in culture and present some evidence for their carcinogenicity in mice and hamsters following topical, subcutaneous, intratracheal and intragastric administration. 6 of the most abundant mutagenic compounds present in morphine pyrolysate were isolated and purified by high-performance liquid chromatography and characterized by gas chromatography/mass spectrometry and 1H-Fourier transform nuclear magnetic resonance spectroscopy. These hitherto unknown compounds, all containing a hydroxy-phenanthrene moiety, were identified as: 3-methyl-3H-naphth[1,2-e]indol-10-ol; 1,2-dihydro-3-methyl-3H-naphth[1,2-e]indol-10-ol; 6-methylaminophenanthren-3-ol; 2-methylphenanthro[3,4-d] [1,3]oxazol-10-ol; 2,3-dimethyl-3H-phenanthro[3,4-d]imidazol-10-ol and 2-methyl-3H-phenanthro[3,4-d]imidazol-10-ol. Mutagenicity in Salmonella typhimurium TA98 of these compounds increased in the order listed, the last compound being 35 times more active than benzo[a]pyrene. The mechanisms, by which these mutagens are formed and metabolically activated are discussed.

Animals↗
PubMedDate not supplied

Detection of carcinogen-DNA adducts in exfoliated urothelial cells of cigarette smokers: association with smoking, hemoglobin adducts, and urinary mutagenicity.

The presence of covalent modifications in DNA obtained from exfoliated urothelial cells of smokers and nonsmokers was determined using 32P postlabeling methods. Urine and blood samples were procured from 73 persons. Cells were removed from the urine by filtration. DNA was isolated using an enzyme-solvent extraction method and then coprecipitated with glycogen. Sufficient DNA to detect 1 carcinogen-DNA adduct/10(9) normal nucleotides was obtained from 40 of the 73 samples. DNA was hydrolyzed to 3'-phosphodeoxynucleotides and then 32P postlabeled under conditions of excess [32P]ATP. Carcinogen-DNA adducts were resolved using anion-exchange thin-layer chromatography and visualized by autoradiography; film exposures lasted as long as 7 days. Twelve different carcinogen-DNA adducts and a diagonal zone of radioactivity could be found, but no sample contained all adducts. At least four adducts appeared to be cigarette smoking related. These adducts were from 2 to 20 times higher in the smokers than the nonsmokers. Two carcinogen-DNA adducts were qualitatively very similar to adducts described earlier in a study of human bladder biopsies. One of these corresponded to N-(deoxyguanosin-8-yl)-4-aminobiphenyl. Adducts were correlated significantly with the levels of 4-aminobiphenyl hemoglobin adducts and number of cigarettes smoked. In addition, levels of the putative N-(deoxyguanosin-8-yl)-4-aminobiphenyl adduct and a measure of total adducts were correlated with the mutagenic activity of the individual's urine. These data suggest that noninvasive, biological monitoring techniques can be applied to the study of carcinogen-DNA adducts in humans at high risk for bladder cancer.

Aminobiphenyl Compounds↗
PubMedDate not supplied

Interstrain comparison of hepatic and renal microsomal carcinogen metabolism and liver S9-mediated mutagenicity in DA and Lewis rats phenotyped as poor and extensive metabolizers of debrisoquine.

Lewis (extensive metabolizers) and DA (poor metabolizers) rat strains show genetic polymorphism for the gene regulating debrisoquine 4-hydroxylation in a manner analogous to human drug polymorphism and show also a different toxicological response to aflatoxin B1. In order to investigate the underlying mechanism(s) of the different drug-metabolizing capacities, the in vitro metabolism and liver S9-mediated mutagenicity of several drugs and carcinogens were studied in female Lewis and DA rat strains, using untreated, 3-methylcholanthrene-treated, and phenobarbital-treated animals. S9-mediated mutagenicity of aflatoxin B1 and hepatic and renal ochratoxin A 4-hydroxylase activity were much lower in DA rats; however, the activity of a number of other hepatic and renal drug-metabolizing enzymes did not show any interstrain difference. Slight strain differences were found in the inducibility of several hepatic drug-metabolizing enzymes, except for ochratoxin A 4-hydroxylase activity; the latter was inducible only by 3-methylcholanthrene in the DA strain and appeared to be linked genetically with other Ah locus-associated monooxygenases. Our data suggest that ochratoxin A 4-hydroxylase activity, which is low in the DA strain, is catalyzed by a cytochrome P-450 isozyme different from that responsible for debrisoquine 4-hydroxylation. Our results provide some insight into why the two metabolic oxidation phenotypes show different susceptibility to cancer induction and to the toxicity of certain environmental carcinogens, such as aflatoxin B1 and ochratoxin A.

2-Acetylaminofluorene↗
PubMedDate not supplied

In vivo nitrosoproline formation and other risk factors in Costa Rican children from high- and low-risk areas for gastric cancer.

The hypothesis that intragastric synthesis of N-nitroso compounds (NOC) in early life could play a role in gastric carcinogenesis was tested by applying the N-nitrosoproline (NPRO) test to about 50 children living in high- and low-risk areas for stomach cancer in Costa Rica. The median values of excretion of NPRO and the sum of three nitrosamino acids (micrograms/12 h urine) were 10-20% of those in adults from other geographical high-risk areas for stomach cancer. The urinary NPRO level after proline intake was higher in children from the high-risk area (P < 0.04) and markedly reduced after ingestion of ascorbic acid together with proline (P < 0.05). NPRO levels on the day of proline intake were highly correlated with levels of nitrate excretion (P < 0.001). Mean levels of total NOC in an aqueous (pH 2) extract of cooked beans from the high- and low-risk areas were similar. Acid-catalyzed nitrosation of the extract increased the total NOC concentration up to 1000-fold, but there was no difference between samples from the two areas. About 10% of bean extracts from both areas showed weak direct-acting genotoxicity in Escherichia coli; after acid-catalyzed nitrosation, all samples were genotoxic at similar levels. The diet of children in the low-risk area satisfied recommended levels of intake of energy and most nutrients except riboflavin and retinol equivalents. Diets from the high-risk area were deficient in energy intake and all nutrients except protein and vitamin C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗