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Biomedical subjects

B L Pool

Publications and source records attributed to B L Pool.

9 recordsLinked to original sources
PubMed1990

Employment of adult mammalian primary cells in toxicology: in vivo and in vitro genotoxic effects of environmentally significant N-nitrosodialkylamines in cells of the liver, lung, and kidney.

This report focuses on the use of freshly isolated primary mammalian cells from different tissues and organs of the rat for the rapid and efficient analysis of toxic and genotoxic chemicals. The cells are either treated in vitro or they are isolated from treated animals. Viability by trypan blue exclusion and DNA damage as single-strand breaks are monitored in either case. Therefore, it is possible to compare in vitro and in vivo results directly. N-nitrosamines with unique organ-specific modes in carcinogenesis were studied in vitro using hepatocytes derived from three species (rat, hamster, and pig) and in rat lung and kidney cells. The sensitive detection of all carcinogenic nitrosamines was achieved, although a pattern of cell-specific activation was not observable. The new modification of the in vivo approach allowed the sensitive detection of NDMA genotoxicity in hepatic and in extrahepatic tissues. It is important to point out that the method is an efficient tool for toxicokinetic studies with genotoxic carcinogens in vivo.

Animals↗
PubMed1990

Assay-specific genotoxicity of N-nitrosodibenzylamine to the rat liver in vivo.

N-Nitrosodibenzylamine (NDBzA) is mutagenic to Salmonella typhimurium and induces DNA strand breaks in isolated rat hepatocytes, yet it is reported to be non-carcinogenic to the rat. Here we report that it is inactive in both the rat and mouse bone marrow micronucleus assays and in a rat liver autoradiographic assay for unscheduled DNA synthesis. It is, however, clearly active as a micronucleus-inducing agent and mitogen in the rat liver and is capable of inducing single-strand breaks in the DNA of rat liver. The origin and implications of this curious conflict of in vivo genotoxicity data are discussed. Irrespective of that discussion, it is concluded that NDBzA is genotoxic to the rat liver in vivo.

Animals↗
PubMed1990

Organ specific genotoxicity and carcinogenicity.

1. The in vitro studies showed that organ specific metabolic activation does not appear to play a predominant role for the in vivo activities of the studied nitrosamines 2. The in vivo studies following 1 h exposure of rats with the nitrosamines can differentiate between organs susceptible for genotoxicity and and those which are not. Nontarget organs in carcinogenicity can not be identified exclusively. 3. The additional study of persistence of genotoxicity may identify organs susceptible for carcinogenicity. Presently, we are working on new techniques to detect DNA SSB and other events with microscale methods. This is necessary to allow a more complete elucidation of genotoxicity in remote target organs and with other carcinogens which may not induce DNA SSB. Accordingly in the near future we expect to have even more versatile tools available to study toxicokinetics of foreign compound. Meanwhile our work with N-nitrosamines is continuing in order to better understand their in vivo modes of action and to better evaluate their burden and risk for man.

Animals↗
PubMed1989

DNA amplification in genetic toxicology.

Chemical compounds can cause amplification of specific DNA sequences. DNA amplification may result in an enhanced production of gene products which help cells to cope with the chemicals. This may lead to a resistance of the cells toward the agent. Additionally, initiation of transformation or progression of transformed cells to tumorigenicity may also involve DNA amplification. Therefore, it is of interest to study the potential of chemicals to induce DNA amplification. This report focuses on the investigation of a variety of chemicals in 2 systems with which the amplification of viral DNA is measured within cells in culture. One model system comprises the measurement of SV40 DNA content in an SV40-transformed Chinese hamster cell line following chemical treatment. Antitumor agents as well as genotoxic and non-genotoxic compounds were studied in this system as a first step to determine the DNA amplification-inducing potential of a variety of differently acting chemical compounds. Also, a novel assay based on adeno-associated virus infection of cells is described. This system may offer the possibility of studying DNA amplification in a variety of different target cells. For the future, the need is stressed to develop and analyze versatile systems to study amplification of specific target genes in untransformed cells and in tumor cells.

Animals↗
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↗