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R Mermelstein

Publications and source records attributed to R Mermelstein.

At least 37 records · Page 2Linked to original sources
PubMed1985

Genetic and quantum chemical basis of the mutagenicity of nitroarenes for adenine-thymine base pairs.

The mutagenicity of nitroarenes for Salmonella typhimurium strains with adenine-thymine base pairs at the mutational site is dependent upon enzymic reduction of the nitro function. Although the electrophilic metabolites of nitroarenes are capable of mutating adenine-thymine base pairs, they show a marked preference for guanine-cytosine pairs when given a choice. Quantum chemical calculations indicate the reactivity order for nucleophilic sites in an AT run of base pairs to be the N-7 of adenine (N7(A)) first, followed by an approximately equal reactivity for C-8 of adenine (C8(A)) and O4 of thymine (O4(T)). Given the low probability of reaction of electrophilic metabolites of nitroarenes with adenine-thymine base pairs, the mutagenic potency of nitroarenes for strains with adenine-thymine base pairs at the mutational site is remarkable.

Adenine↗
PubMed1983

5-Nitroacenaphthene: a newly recognized role for the nitro function in mutagenicity.

The direct-acting mutagenicity of 5-nitroacenaphthene for Salmonella typhimurium is dependent upon the reduction of the nitro function as evidenced by the significant decrease in mutagenicity seen with nitroreductase-deficient Salmonella strains. Addition of microsomal preparations results in a significant increase in mutagenicity and a by-passing of the block in nitroreductase-deficient and arylhydroxylamine esterifying-deficient enzyme strains. The results are taken to indicate that the microsome-induced mutagenicity is due primarily to oxidation of the acenaphthene moiety. The results are consistent with recent studies which indicate that the nitro function exercises a directing effect on ring oxidation.

Acenaphthenes↗
PubMed1983

Mutagenicity and genotoxicity of nitroarenes. All nitro-containing chemicals were not created equal.

The nitrated polycyclic aromatic hydrocarbons constitute a group of chemicals of environmental concern which display a broad spectrum of mutagenic, genotoxic and carcinogenic properties. Some members of the group are the most potent direct-acting bacterial mutagens while others exhibit low levels of potencies which require metabolic activation mixtures. Bacterial mutagenicity is dependent upon reduction of the nitro function. In mammalian cell systems the genetic and genotoxic effects of these nitrated chemicals include the induction of unscheduled DNA synthesis, sister-chromatid exchanges, chromosomal aberrations, gene mutations and cell transformation. The qualitative as well as quantitative expression of these effects is dependent upon the species and tissue of origin as well as culture history of the cell which in turn determine their enzymic capabilities and the conversion of these nitroarenes to ultimate mutagens and genotoxicants. In eukaryotic cells the following bioactivation pathways have been recognized: (a) reduction of the nitro moiety, (b) ring oxidation (the nature of which is influenced by the nitro function) followed by reduction of the nitro group, and (c) ring oxidation without concomitant reduction of the nitro moiety.

Animals↗
PubMed1983

Apparent absence of recombinogenic activity of nitropyrenes for yeast.

Nitropyrenes have been shown to be potent bacterial and mammalian mutagens. However, they failed to induce any recombinogenic activity in Saccharomyces cerevisiae D4 even at elevated concentrations and following extended periods of exposure. A plausible explanation for this lack of activity is the absence or the lack of activation of the enzyme required for the activation of nitropyrenes in this test system under the experimental (aerobic) conditions employed.

Genes↗
PubMed1983

Evidence that nitroarene metabolites form mutagenic adducts with DNA-adenine as well as with DNA-guanine.

Nitropyrenes as well as several other nitroarenes and their metabolites exhibit considerable mutagenicity for Salmonella tester strains (TA102 and TA96) which have adenine-thymine base pairs at the mutational target. This finding is unexpected as previous biochemical studies had shown that arylation at the C8 position of DNA-guanine is the only chemically and biologically significant reaction. This conclusion is supported by the extraordinary mutagenic potency of these chemicals in Salmonella strains with guanine at the mutational site (e.g., TA98). The present results indicate that a minor reaction with DNA-adenine may result in the formation of an unusually potent promutagenic DNA adduct.

Adenine↗
PubMed1983

Semantic congruity and expectancy in symbolic judgments.

These experiments assess the degree to which the semantic-congruity effect in comparative judgment can be explained by such expectancy effects as priming, perceptual "set," or strategies used in the task. The first experiment mixed a lexical-decision task with the comparative-judgment task and showed that neither automatic semantic priming nor deliberate preparation can account for the congruity effect. Experiments 2-4 assessed expectancy effects in a different way by presenting the instructions for comparative judgment either before or after the pair to be judged. These experiments included, among other things, a number of safeguards against artifacts in this paradigm. In these three experiments the congruity effect was obtained with both orders of stimuli and instructions, contrary to the prediction of an expectancy hypothesis. The results indicate that when stimuli are not degraded. The semantic-congruity effect depends largely on the relation between the stimuli and the instructions and only to a small degree, if at all, on expectancy.

Cues↗
PubMed1982

The chemical activation of non-mutagenic nitrated polycyclic aromatic hydrocarbons to mutagens.

Nitrated polycyclic aromatic hydrocarbons, including carcinogens, may be non-mutagenic in microorganisms because bacterial nitroreductases are unable to reduce their nitro function to proximate mutagenic hydroxylamines. This reduction of the nitro moiety can be accomplished chemically in situ using zinc dust. The procedure, which is compatible with the Salmonella mutagenicity assay, was used to generate mutagens from chemicals which otherwise are non-mutagenic even in the presence of microsomal preparations.

Carcinogens↗
PubMed1982

Evidence for the existence of distinct nitroreductases in Salmonella typhimurium: roles in mutagenesis.

Previous studies on the mutagenicity of nitroheterocyclics and nitrated polycyclic aromatic hydrocarbons had indicted the probable existence in Salmonella typhimurium of a multiplicity of nitroreductase activities of varying specificities which are required for the expression of the mutagenicity of nitro-containing chemicals. In the present study evidence is presented that these activities reside in different gene products: (a) strains totally lacking in the nitroreductase which recognizes niridazole and related substances are not mutagenized by this group of chemicals and yet they are fully responsive to the mutagenic action of dinitropyrenes; (b) double mutants which have lost both types of specificities can be constructed. Finally, the presence of a third type of nitroreductase with a specificity for 4-nitroquinoline-1-oxide is implied by the finding that the nitroreductase-deficient strains described herein retain full sensitivity to the mutagenic action of this chemical.

Mutagens↗
PubMed1981

Evidence for the existence of a family of bacterial nitroreductases capable of activating nitrated polycyclics to mutagens.

A derivative of Salmonella typhimurium TA98 which does not respond to the potent mutagenicity of 1,8-dinitropyrene is described. This novel strain also shows a lack of response to the mutagenic action of 1,3-dinitropyrene and a greatly reduced response to 1,6-dinitropyrene and 1-nitropyrene. The responses to 1,3,6-trinitropyrene and 1,3,6,8-tetranitropyrene are affected to a much lesser extent. This strain (TA98/1,8DNP6) is fully sensitive to the mutagenicity of 4-nitroquinoline-1-oxide, niridazole, nitroacridine, and nonnitrated frameshift mutagens. This strain appears to be deficient in a nitroreductase which reduces nitrated pyrenes and possibly other nitrated polycyclic aromatic hydrocarbons to corresponding hydroxylamines, the penultimate mutagens.

Animals↗
PubMed1981

Structural basis of the mutagenicity in bacteria of nitrated naphthalene and derivatives.

While 2-nitronaphthalene was a weak direct-acting base-substitution mutagen (1.4 revertants/nanomole) for Salmonella typhimurium, the analogous nitronaphthalic acid anhydride and imides were moderate frameshift mutagens (approximately 20 rev/nanomole in strain TA98). Although imide derivatives are efficient DNA intercalators, mutagenicity data indicate that the bulk of the frameshift activity is derived from adduct formation between hydroxylamine intermediates and DNA. The low level of frameshift activity (approximately 8% of total) resulting from simple intercalation (measured in strain TA 1537) is not dependent upon reduction of the nitro function. Evidence is presented that suggests that the reduction of the nitro function to the corresponding hydroxylamine might not involve a free nitroso intermediate. The introduction of a second nitrofunction into nitronaphthalenes results in great positional effects of the various isomers on mutagenic activity and specificity.

Mutagens↗