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C Malaveille

Publications and source records attributed to C Malaveille.

At least 73 records · Page 4Linked to original sources
PubMed1986

Monoclonal antibody-directed analysis of cytochrome P-450-dependent monooxygenases and mutagen activation in the livers of DBA/2 and C57BL/6 mice.

Monoclonal antibodies (MAb 1-7-1 and Mab 2-66-3) specific for cytochrome P-450 (cyt. P-450) isozymes inhibited the metabolism of carcinogens, other xenobiotics, and endogenous compounds in two strains of mice. Postmitochondrial liver supernatant (S9) was prepared from untreated, 3-methylcholanthrene-treated, phenobarbital-treated, and pregnenolone 16 alpha-carbonitrile-treated C57BL/6 (B6) and DBA/2 (D2) mice. The modifying effect of two types of MAb to a 3-methylcholanthrene-induced cyt. P-450 and a phenobarbital-induced cyt. P-450 was investigated for: (a) S9-mediated mutagenicity of aflatoxin B1, benzo(a)pyrene 7,8-dihydrodiol, 2-acetylaminofluorene, and N-nitrosomorpholine in Salmonella typhimurium strains; and (b) the activity of aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase, aminopyrine N-demethylase, and testosterone 6 beta-, 7 alpha-, and 16 beta-hydroxylases. With certain S9s, MAb-1-7-1 inhibited only those cytochrome P-450 isozymes involved predominantly in activity of aryl hydrocarbon hydroxylase, ethoxyresorufin O-deethylase, and ethoxycoumarin O-deethylase and mutagenicity of 2-acetylaminofluorene and benzo(a)pyrene 7,8-dihydrodiol; MAb 2-66-3 inhibited only those involved in aminopyrine N-demethylase and testosterone 6 beta-, 7 alpha, and 16 beta-hydroxylase activity and aflatoxin B1 mutagenicity. Both Mab 1-7-1 and MAb 2-66-3 inhibited cytochrome P-450 isozyme(s) implicated predominantly in testosterone 7 alpha-hydroxylation in S9 from pregnenolone 16 alpha-carbonitrile-treated B6 mice. MAb 1-7-1 did not inhibit N-nitrosomorpholine mutagenicity and MAb 2-66-3 increased it by 2- to 6-fold depending on the source of S9. Using these MAbs, it is thus possible to identify the contribution of the epitope-defined single or class of cyt. P-450 to specific metabolic reactions in S9 from untreated and inducer-treated mice.

Animals↗
PubMed1985

Destruction of aromatic amines in laboratory wastes through oxidation with potassium permanganate/sulfuric acid into non-mutagenic derivatives.

Nine aromatic amines, i.e., benzidine; o-tolidine; o-dianisidine; 3,3'-dichlorobenzidine; 4-aminobiphenyl; 1- and 2-naphthylamine; 4,4'-methylene bis(2-chloroaniline) and m-toluenediamine, were oxidized with potassium permanganate/sulfuric acid. Experimental conditions for complete degradation of these aromatic amines are described. The disappearance of the parent compound through oxidation was measured using HPLC coupled with UV spectrophotometry. The corresponding degradation products were found to be non-mutagenic to Salmonella typhimurium strains TA100, TA98 and TA97, both in the presence and absence of a rat liver S9 activation system. A collaborative study, involving 11 laboratories, has shown the applicability and the reproducibility of this degradation method.

Amines↗
PubMed1984

Lack of mutagenicity of synthetic pyrethroids in Salmonella typhimurium strains and in V79 Chinese hamster cells.

Seven pyrethroids, i.e., cypermethrin, permethrin, deltamethrin, bioresmethrin, resmethrin, cismethrin and fenvalerate, were not found to be mutagenic in (a) Salmonella typhimurium strains TA100 or TA98 in the presence or absence of a rat liver activation system using the plate incorporation assay and fluctuation tests, or (b) V79 Chinese hamster cells in the presence or absence of hepatocytes.

Animals↗
PubMed1984

Possible involvement of a vicinal, non-bay-region dihydrodiol-epoxide in the activation of dibenzo[a,e]fluoranthene into bacterial mutagens.

Dibenzo[a,e]fluoranthene, its 7-hydroxy, 3,4- and 12,13-dihydrodiol metabolic derivatives as well as three synthetic, structurally related hydrocarbons, were tested for mutagenicity towards Salmonella typhimurium TA100 strain in the presence of 3-methylcholanthrene-treated rat and mouse liver post-mitochondrial supernatants. Of these compounds, the 12,13-dihydrodiol showed the highest activity, being 6-10 times more mutagenic than the parent compound. Our data, in conjunction with those of previous studies on the liver microsomal metabolism and DNA binding of dibenzo[a,e]fluoranthene and its dihydrodiols, indicate that activation of dibenzo[a,e]fluoranthene to bacterial mutagens may occur predominantly through a vicinal, non-bay-region 12,13-dihydrodiol epoxide.

Animals↗
PubMed1984

Destruction of carcinogenic and mutagenic N-nitrosamides in laboratory wastes.

The chemical degradation of five N-nitrosamides used widely for the experimental induction of cancer has been studied with the goal of identifying, and experimentally validating, reliable methods that can be recommended for the destruction of carcinogenic N-nitrosoureas and related compounds in laboratory wastes. Although data are not yet complete, preliminary evidence indicates that none of the five methods studied thus far is ideal for hazard-control purposes. Decomposition with 1 mol/L potassium hydroxide solution destroyed the N-nitrosamides, but generated diazoalkanes, which are carcinogenic, toxic and potentially explosive. Treatment with strong acid in the presence of sulfamic acid or iron filings completely decomposed all N-nitrosamides without forming diazoalkanes, but failed in the presence of solvents which were immiscible with water. Cleavage with hydrogen bromide in glacial acetic acid proceeded to a point of maximum degradation, following which gradual reformation of the N-nitrosamide was observed; this resynthesis could be avoided by carefully bubbling nitrogen through the reaction mixture, but degradation was slow or failed completely in the presence of hydroxylic solvents. Permanganate oxidation was effective in sulfuric acid solution, but was incomplete when an alcohol or dimethyl sulfoxide was present. Salmonella typhimurium tester strains TA1535, TA1530 and TA100, which detect base-pair substitutions in DNA, detected mutagenic degradation products in each of the destruction methods, with the exception of the hydrobromic acid/acetic acid procedure.

Carcinogens↗
PubMed1983

Preparation of aflatoxin B1-BSA conjugate with high hapten/carrier molar ratio.

We reported previously on the properties of an anti-aflatoxin B1 (AFB) antiserum raised with a conjugate in which AFB is coupled at the C8 position to bovine serum albumin (BSA). The hapten/carrier protein molar ratio of the conjugate was 14. We have since been able to optimize the coupling conditions, resulting in the preparation of another conjugate, with a molar ratio of 45. Comparison of the 2 conjugates by double-gel immunodiffusion analysis shows that little BSA 'activity' remains on the conjugate with a high molar ratio; on the other hand, its capacity to precipitate in the presence of anti-AFB antibodies is increased.

Aflatoxin B1↗
PubMed1983

Interrelationships in mice of antipyrine half-life, hepatic monooxygenase activities and liver S9-mediated mutagenicity of aflatoxin B1, benzo[alpha]pyrene 7,8-dihydrodiol, 2-acetylaminofluorene and N-nitrosomorpholine.

To evaluate the predictive value of serum antipyrine half-life AP(T1/2) as an index of hepatic carcinogen metabolism, groups of C57BL/6 and DBA/2 mice were treated with various inducers and inhibitors of cytochrome P-450-dependent monooxygenases (pregnenolone-16 alpha-carbonitrile (PCN), phenobarbital (PB), 5,6-benzoflavone (5,6-BF), 3-methylcholanthrene (MC), disulfiram (DIS), 7,8-BF). Groups of mice were also given ethanol (3% in drinking water) for 12 days. Within each group, mean serum AP-(T1/2) was compared with (i) the in vitro activity of hepatic microsomal benzo[alpha]pyrene (BP) 3-hydroxylase, 2-acetylaminofluorene (AAF)-N-hydroxylase and aldrin monooxygenase, and (ii) the liver S9-mediated mutagenicity of aflatoxin B1 (AFB), trans-7,8-dihydro-7,8-dihydroxybenzo[alpha]pyrene (BP 7,8-diol), 2-acetylaminofluorene and N-nitrosomorpholine (NMOR) in Salmonella typhimurium strains. Serum AP(T1/2) was only correlated negatively with the activity of BP 3-hydroxylase (P less than 0.001) and aldrin monooxygenase (P less than 0.001). No statistically significant correlation was found between serum AP(T1/2) and liver S9-mediated mutagenicity for any of the four carcinogens. On the basis of these results, we conclude that serum AP(T1/2) may not be a reliable index of the capacity of liver to convert carcinogens into reactive intermediates.

2-Acetylaminofluorene↗
PubMed1983

Quantitative comparison of carcinogenicity, mutagenicity and electrophilicity of 10 direct-acting alkylating agents and of the initial O6:7-alkylguanine ratio in DNA with carcinogenic potency in rodents.

The quantitative relationship between carcinogenicity in rodents and mutagenicity in Salmonella typhimurium was examined, by using 10 monofunctional alkylating agents, including N-nitrosamides, alkyl methanesulfonates, epoxides, beta-propiolactone and 1,3-propane sultone. The compounds were assayed for mutagenicity in two S. typhimurium strains (TA1535 and TA100) and in plate and liquid assays. The mutagenic activity of the agents was compared with their alkylating activity towards 4-(4'-nitrobenzyl)pyridine and with their half-lives (solvolysis constants) in an aqueous medium. No correlations between these variables were found, nor was mutagenic activity correlated with estimates of carcinogenicity in rodents. There was a positive relationship between carcinogenicity and the initial ratios of 7-:O6-alkylguanine formed or expected after their reaction with double-stranded DNA in vitro. The results suggest that alkylation of guanine at position O6 (or at other O atoms of DNA bases) may be a critical DNA-base modification that determines the overall carcinogenicity of these alkylating agents in rodents.

Alkylating Agents↗
PubMed1983

Hydroxylation and nitroreduction are required to activate dimethylnitramine into alkylating and mutagenic agents.

Dimethylnitramine (DMNO) was shown to undergo hydroxylation in the presence of 9000 g supernatant from rat liver (S9) to yield hydroxymethyl-methylnitramine (OH-MNO). OH-MNO displayed a 100-fold higher mutagenic activity in Salmonella typhimurium TA100 strain than DMNO, when compared on a molar basis. The mutagenicity of DMNO in TA100 strain in the presence of S9 paralleled the production of OH-MNO. Acetoxymethyl-methylnitramine (Ac-MNO) and methylnitramine (MNO), two synthetic derivatives of DMNO, were also investigated. Ac-MNO was found to be mutagenic in TA100 strain only in the presence of S9, probably through the release of OH-MNO catalysed by esterase(s); under similar conditions, MNO showed no mutagenicity or toxicity to TA100 strain. OH-MNO showed no alkylating activity towards nicotinamide. These findings implicate OH-MNO as a proximate mutagenic metabolite of DMNO. DMNO and Ac-MNO were found to be more mutagenic in a nitroreductase(s)-proficient (TA100) than in a deficient (TA100 NR) strain. After reduction of OH-MNO with Zn/NH4Cl, it yielded an agent(s) which alkylated nicotinamide. The latter results imply a reduction of the nitro group in OH-MNO to yield a hydroxylamino derivative as the ultimate (or penultimate) mutagenic metabolite. The enzymes and reactive intermediates that may be involved in the activation of DMNO are discussed.

Alkylating Agents↗
PubMed1983

Studies on the efficiency of the Salmonella/rat hepatocyte assay for the detection of carcinogens as mutagens: activation of 1,2-dimethyl-hydrazine and procarbazine into bacterial mutagens.

Aflatoxin B1, benzo[a]pyrene, N-nitrosomorpholine, procarbazine (PC) and 1,2-dimethylhydrazine (DMH) were used to investigate the efficiency of the Salmonella/rat hepatocyte assay for detecting carcinogens as mutagens. In this assay, bacteria and the test compound were co-incubated with freshly isolated rat hepatocytes and then plated onto minimal glucose agar. Factors for optimal mutagenicity, including the number of hepatocytes and the number of bacteria, the type of assay medium and the length of incubation in liquid medium were investigated. All the compounds were metabolized into bacterial mutagens. Mediation of the mutagenicity of PC and DMH by rat hepatocytes indicates that freshly isolated cells of this type are a useful alternative metabolic activation system for use in screening chemicals found to be non-mutagenic in the Salmonella/microsome assay.

1,2-Dimethylhydrazine↗
PubMed1982

Mutagens produced by the pyrolysis of opium and its alkaloids as possible risk factors in cancer of the bladder and oesophagus.

Samples of opium pipe scrapings (opium dross, called sukhteh locally), but not of crude opium, collected in an area with a high incidence of oesophageal cancer in north-east Iran, were shown to contain pro-mutagens, producing mostly frameshift mutations in Salmonella typhimurium strains TA1538 and TA98 after metabolic activation. Pyrolysis of opium and of its major alkaloid, morphine, yielded smoke condensates with mutagenic activities 10 and 100 times higher, respectively, than that of the sukhteh samples tested. Heterocyclic aromatic hydrocarbons and primary aromatic amines present at different concentrations in these three pyrolysates are considered to be the major active principles. Opium addiction has been implicated as a risk factor in bladder cancer in humans and the ingestion of opium pyrolysates, in conjunction with dietary deficiencies, may be related to the high incidence of oesophageal cancer in north-east Iran, although causality has not been established.

Alkaloids↗