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B L Pool

Publications and source records attributed to B L Pool.

48 records · Page 3Linked to original sources
PubMed1982

Fluoro-substituted N-nitrosamines. 4. Comparative genotoxic activities of N-nitrosodibutylamine and three fluorinated analogues in two bacterial systems.

N-Nitrosodibutylamine (NDBA) and three fluorinated analogues (N-nitroso (4,4,4-trifluorobutyl-amine, F3NDBA; N-nitrosobis (4,4,4-trifluorobutyl)amine, F6NDBA; and N-nitrosobis (2,2,3,3,4,4,4-heptafluorobutyl) amine, F14NDBA were comparatively investigated for biological activity in two bacterial systems. Opposite orders of magnitude were obtained for their potency in the two tests. For inducing his+ reversion in auxotrophic strains of Salmonella typhimurium the sequence was F3NDBA greater than F6NDBA greater than NDBA and for inducing lethal DNA damage in repair deficient strains of Escherichia coli WP2 it was NDBA greater than F6NDBA. F14NDBA was not active in either test system.

Animals↗
PubMed1982

In-vitro metabolism of fluorinated diakylnitrosamines.

To elucidate differences in metabolism caused by fluorination of NDEA and NDBA, these compounds and their fluorinated analogs (NDEA-F3, NDEA-F6, NDBA-F3, NDBA-F6 and NDBA-F1 4) were incubated with rat liver microsomal fractions. Aldehydes, nitrite and unchanged nitrosamines were determined. Additionally, the mutagenicity was investigated with a Salmonella/mammalian microsome assay. NDEA-F6 and NDBA-F1 4 were not appreciably metabolized and were not mutagenic. NDEA, NDEA-F3, NDBA, NDBA-F3 and NDBA-F6 were dealkylated and, to a lesser extent, denitrosated. Dealkylation at the fluorinated alkyl group was inhibited, especially in the case of NDEA-F3. Whereas NDEA, NDBA, NDBA-F3 and NDBA-F6 were clearly mutagenic, mutagenicity of NDEA-F3 was only marginal.

Animals↗
PubMed1981

Investigations on the mutagenicity of primary and secondary alpha-acetoxynitrosamines with Salmonella typhimurium: activation and deactivation of structurally related compounds by S-9.

alpha-Acetoxynitrosamines may serve as model compounds to study mechanisms of action of N-nitrosamines. They are readily cleaved through hydrolysis, or by esterases, to yield the same ultimate, reactive species presumably also arising after metabolic activation of N-nitrosamines, Structure-activity investigations on alpha-acetoxynitrosamines promise to aid in elucidating mechanisms involved during the activation of N-nitrosamines. A series of alpha-acetoxyalkynitrosamines was therefore tested for mutagenicity with Salmonella typhimurium TA 1535. The compounds were readily cleaved, by hydrolysis, to mutagenic intermediates. When comparing compounds according to their proposed alkylating properties, unstable secondary alpha-acetates were considerably more mutagenic than the corresponding relatively stable primary alpha-acetates. Addition of S-9 mix caused both activation as well as deactivation in an unexpected structure-related pattern. This was so because an exactly opposite influence of S-9 components on the mutagenicity was observed for each pair of primary and secondary compounds containing the same alkylating spices. Furthermore, pairs of compounds with both methylating and ethylating properties were differently influenced by S-9 addition than those with propylating or butylating effects. This clearly demonstrates how different chemical properties of intermediate forms may strongly influence the biological activity of otherwise quite similar compounds.

Aldehydes↗
PubMed1980

Mutagenicity--relevance of short-term tests.

Short-term tests measuring diverse biological activities of compounds, such as mutagenicity, have been proposed as prescreening methods to determine potential carcinogenicity. High correlations of up to 90% have been found for response in short-term tests versus response in long-term carcinogenicity assays, e.g. for the Salmonella-microsome method developed by Ames and also for the cell transformation test developed by Styles. How these short-term assays may be suited to predict potential carcinogenicity of N-nitrosamines is described. Data on how the mutagenicity of N-nitrosamines in the Salmonella-microsome assay compares to their carcinogenicity shows that correlation factors as high as 90% have not necessarily been obtained. The reasons for this apparent lack of correlation as well as which valuable role the short-term assays play in other fields of chemical carcinogenesis is discussed.

Cell Transformation, Neoplastic↗
PubMed1979

Microsomal mediated metabolism of dialkylaryltriazenes. I. Demethylation of ring halogenated 3,3-dimethyl-1-phenyltriazenes.

The oxidative N-demethylation was investigated for a series of 3,3-dimethyl-l-phenyl-triazenes. Triazenes, deactivated with halogene atoms in the phenylring, were expected to be better demethylated. The results do indicate a good trend that substitution of the ring with deactivating atoms and extent of demethylation compare well. The percentages of demethylation were: For 3,3-dimethyl-l-phenyltriazene, 45%; for 3,3-dimethyl-l (4-chlor-phenyl)-triazene, 92%; for 3,3-dimethyl-l(4-bromophenyl)triazene, 89%; for 3,3-dimethyl-l-(2,4,6-trichlorophenyl)triazene, 122%; and for 3,3-dimethyl-l-l-(2,4,6-tribromophenyl)triazene, 85%.

Animals↗
PubMed1979

Microsomal mediated metabolism of dialkylaryltriazenes. II. Isolation and identification of metabolites of 3,3-dimethyl-1-phenyltriazene.

After incubating 3,3-dimethyl-1-phenyltriazene with rat liver microsomes, acetanilid and derivatives of aniline and possibly of 3-methyl-1-phenyltriazene were found as metabolites and identified by mass spectrometry. This is the first time that directly formed metabolites (other than formaldehyde) of a dialkyltriazene were identified. The isolation of a derivative of 3-methyl-1-phenyltriazene as 3-acetyl-3-methyl-1-phenyltriazene supports other evidence that the triazenes are enzymically demethylated. Indication for the formation of phenylhydrazine was also obtained. In addition, hydrolysates of the polar fractions of the incubation mixture contained aniline and 4-hydroxy-aniline as a aglycones.

Acetanilides↗
PubMed1979

Carcinogenicity and mutagenicity testing of three isomeric N-nitroso-N-methylaminopyridines in rats.

Three isomeric N-nitroso-N-methylaminopyridines (NMPY's) were investigated for their carcinogenic activity in BD VI rats following chronic oral administration and for their mutagenic properties in the Ames assay. On the basis of postulated reaction mechanisms, it was expected that 3-NMPY would react differently than 2- and 4-NMPY, but the outcome of both carcinogenicity and mutagenicity assays did not show this. 2-NMPY induced tumors of the esophagus and possibly also of the liver; 3- and 4-NMPY had no activity as carcinogens under the experimental conditions used. Similarly, high concentrations of 2-NMPY showed mutagenic activity toward Salmonella typhimurium TA100, whereas 3- and 4-NMPY did not have such an effect.

Aminopyridines↗
PubMedDate not supplied

Metabolic activation capabilities of S9 and hepatocytes from uninduced rats to convert carcinogenic N-nitrosamines to mutagens.

6 carcinogenic nitrosamines were studied in Salmonella typhimurium TA1535 after activation by S9 and by hepatocytes. All nitrosamines were activated by S9 from induced rats, regardless of their organotropy. The hepatocarcinogenic nitrosamines (N-nitrosodimethylamine, NDMA; N-nitrosodiethylamine, NDEA; N-nitrosomorpholine, NM and N-nitrosodibutylamine, NDBA) were activated to mutagens by S9 and by hepatocytes both derived from noninduced rat livers, NDMA and NM inducing more his+ revertants in the presence of hepatocytes. The oesophageal carcinogenic nitrosamine N-nitrosomethylbenzylamine (NMBeA) and bladder organotrophic N-nitroso(4-hydroxybutyl)butylamine(NBBOH) were neither converted by liver preparations of uninduced rats into mutagenic intermediates nor by hepatocytes. This study indicates that isolated cells derived from untreated animals may be better suited to study liver specific activation in vitro than disrupted subcellular metabolizing systems from induced animals.

Animals↗
PubMedDate not supplied

Detection of mutations in bacteria and of DNA damage and amplified DNA sequences in mammalian cells as a systematic test strategy for elucidating biological activities of chemical carcinogens.

The interdisciplinary evaluation of risks from carcinogens utilizes, inter alia, data on the activities of the compounds in short-term assays. A systematic approach is being used to determine mutagenesis in bacteria (the study of direct activities and specific modes of metabolic activation), DNA damage within primary mammalian cells (DNA single-strand breaks and persistence of damage, by a method extendable to the in vivo situation) and amplified DNA sequences in cultured cells (as an endpoint probably relevant to carcinogenesis). This test combination was expected to reduce some of the shortcomings of other batteries of tests, which suffer from a lack of appropriate metabolic conversion of compounds, irrelevancy of genetic endpoints and pharmacokinetic limitations. Furthermore, as each assay in the test strategy differs from the others only by one of the parameters described above, a reasonable understanding of divergent test results from assay to assay was anticipated. Several substances were investigated to elucidate why their activities in short-term assays and in carcinogenesis experiments do not correlate. The substances were N-nitrodimethylamine, for which formaldehyde is the reactive intermediate in bacterial mutagenesis but not in mammalian cells or in vivo, N-nitrosodiethanolamine, a carcinogen that must be activated by external alcohol dehydrogenase to be mutagenic in bacteria, N-nitrosodialkylamines, with unique organotropism in vivo for which organ-specific activation was studied in vitro, N-nitroso compounds that are inactivated in vivo but not in vitro, and components of the aristolochic acid mixture which may be metabolized oxidatively or reductively, as well as numerous miscellaneous compounds that were expected to be genotoxins on account of their chemical structure. In addition to the assessment of genotoxicity, the results obtained in individual tests of this strategy yield important data on mechanisms of activity, such as organ-specific activation and deactivation, species variations, in vitro/in vivo correlation and persistence or repair of damage.

Animals↗