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Biomedical subjects

N M Trieff

Publications and source records attributed to N M Trieff.

At least 19 recordsLinked to original sources

Cytogenetic, developmental, and biochemical effects of aluminum, iron, and their mixture in sea urchins and mussels.

The present study was undertaken to evaluate the toxicity of aluminum sulfate, ferric chloride and their 1:1 mixture (Mix) on early development, fertilization and offspring quality in three sea urchins species (Sphaerechinus granularis, Paracentrotus lividus, Psammechinus microtuberculatus) and in mussels (Mytilus galloprovincialis). The endpoints were the following: a) larval malformations; b) developmental arrest; c) embryonic mortality; d) fertilization success; e) cytogenetic effects, and f) luminol-dependent chemiluminescence (LDCL). Overall data point to the induction of developmental defects in both sea urchin and mussel embryos following exposure of embryos to Al(III) or Fe(III) (10(-7) to 10(-6) M), whereas Mix caused varied effects vs. Al(III) or Fe(III) alone, from scarce or no additive effects (M. galloprovincialis and P. lividus) to a dramatic rise in embryolethality even at nominal levels of 10(-8) M (Ps. microtuberculatus).S. granularis sperm underwent a dose-dependent decrease in fertilization success following exposure to Al(III), or Fe(III), or Mix at levels ranging from 10(-8) to 10(-5) M. A significant increase of developmental defects was observed in the offspring of S. granularis sperm exposed to micromolar levels of the agents, suggesting an Al(III)- and Fe(III)-related transmissible damage to sperm. The cytogenetic analysis of Al(III)-, Fe(III)-, or Mix-exposed S. granularis embryos showed a significant increase in mitotic aberrations. A relevant feature of the observed cytogenetic damage included scattered chromosomes, suggesting cytoskeleton damage. The LDCL emission in S. granularis embryos showed a dose-related inhibition by agent levels ranging from 10(-7) to 10(-5) M; this held true for both spontaneous and, to a larger extent, for horseradish peroxidase (HRP)-activated LDCL. LDCL associated with fertilization was affected by Al(III), Fe(III) and Mix, with a time- and dose-related shift from stimulation to inhibition. The changes observed in LDCL emission suggested that the observed damage to embryogenesis, fertilization and mitotic activity may be related, at least partly, to alterations of the embryo prooxidant state. The present data point to developmental, cytogenetic and biochemical changes related to realistic levels of Al(III), Fe(III) and their mixtures, raising concern as to their environmental, occupational and iatrogenic exposures.

Alum Compounds

Quantification, qualification, and microbial killing efficiencies of antimicrobial chlorine-based substances produced by iontophoresis.

The dependence of microbial killing on chloride ions present in solutions undergoing iontophoresis is addressed. A 400-microA current was applied to vials containing synthetic urine or saline, and the production of chlorine-based substances (CBSs) was detected by the N,N-diethyl-p-phenylene diamine colorimetric method. It was found that as the time of current application increased, the total concentration of CBSs also increased. The iontophoretic current converted (through oxidation) chloride ions present in the solutions into CBSs such as free chlorine, chlorine dioxide, chlorite, monochloramine, and dichloramine (the last two were produced by iontophoresis only when nitrogenous substances were present in the solution). Two of the CBSs (free Cl and ClO2), when they were separately added back to microbial suspensions (approximately 3 x 10(5) CFU/ml) at the same concentrations at which they were detected in either 0.46% (wt/vol) NaCl solution or synthetic urine iontophoresed for 4 h at 400 microA, reduced or eliminated bacterial genera and a fungus. However, when free Cl and ClO2 were jointly added back to microbial suspensions, bacterial and fungal killing was synergistic and more rapid and complete than when these chlorine-based biocides were added separately. Therefore, iontophoresis of solutions containing chloride ions produces chlorine-based biocides that are responsible for the antimicrobial effect of iontophoresis.

Bacteria

In vitro inactivation of glucose-6-phosphate dehydrogenase from human red blood cells by acrolein: a possible biomarker of exposure.

We have investigated the possibility of utilizing glucose-6-phosphate dehydrogenase (G6PD) as a macromolecular (biological) marker of acrolein exposure. The result showed a dose-dependent inactivation of the erythrocyte G6PD in situ or as a purified enzyme from human erythrocytes or yeast. Amino acid analysis on the chemically modified yeast G6PD showed a formation of a lysine adduct which is probably linked to the inactivation.

Acrolein

Prediction of toxicological interactions in a binary mixture by using pattern recognition techniques: proposed approach with a developed model.

A model has been suggested to predict the nature of toxicological interaction in binary mixtures. The approach uses the NLM-HSDB computerized data bases, the ATSDR toxicologic profiles, and other literature for categorizing the nature (synergistic, antagonistic or no interaction) and degree of interaction. Multivariate modeling (pattern recognition techniques) is the statistical approach utilized to separate groups of compounds into those that interact synergistically or antagonistically with a given toxic compound. Preliminary results indicate 1) that there are sufficient data in the literature on interactions to permit such modeling and 2) that in the case of carbon tetrachloride those compounds that interact synergistically with it are more similar to each other than those that interact antagonistically with respect to a number of structural and toxicologic parameters. This suggested approach of utilizing pattern recognition tools will be quite useful for regulatory agencies in predicting toxicological interactions occurring in complex chemical mixtures in the environment.

Carcinogenicity Tests

Aromatic amines and acetamides in Salmonella typhimurium TA98 and TA100: a quantitative structure-activity relation study.

The mutagenicity of a series of 19 aromatic amines had been previously measured in Salmonella typhimurium strains TA98 (frame-shift) and TA100 (base-pair) with the addition of S9 from Aroclor 1254-induced rat liver. A quantitative structure-activity relation (QSAR) study using multiple regression analysis points out the influence of three factors on mutagenicity: lipophilic character, position of the amine group, and whether it is free or acetylated, as expressed by log P and two indicator variables I1 and I2, respectively. The multiple regression equations explain 78 and 88% of the variance in log mutagenicity in TA98 and TA100, respectively. First of all, mutagenicity was shown to increase with lipophilicity. On the other hand, mutagenicity is reduced when the amine or acetamido position is ortho to the juncture because of steric hindrance in its biotransformation compared with a non-ortho isomer. It is decreased also by the acetylation of the amine group, probably because the acetyl group needs to be first split off prior to oxidation of the amine group to -NHOH.

Acetamides

Effects of sodium azide on sea urchin embryos and gametes.

Sodium azide (SA) was tested on sea urchin embryos and gametes (Paracentrotus lividus). Developing embryos were exposed to SA (10(-6) to 10(-3) M) up to pluteus larval stage, or for shorter intervals before or after hatching. Developmental defects in SA-exposed embryos consisted mainly of gut abnormalities, without any detectable differences between pre- or post-hatch-exposed embryos. SA-induced damage to gut was exerted during gastrulation, as evident by lectin binding of extracellular matrix. No mitotic damage was observed in SA-exposed embryos, nor could pH-related variations be detected in SA-induced embryotoxicity at pH's ranging from 8 to 6. Concurrently, no effect ensued in the exposure of unfertilized eggs to SA (10(-5) to 10(-2) M) both in terms of fertilization success and of offspring quality. When sperm were suspended in filtered seawater at pH's ranging from 8 to 6, and SA levels ranging from 10(-5) to 10(-2) M, fertilization success of SA-exposed sperm appeared to be modulated by pH, by displaying three distinct dose-response trends at pH 8, 7, or 6. The consequences of sperm pretreatment on offspring quality failed to show any significant SA-induced changes on larval malformations or mortality, while confirming the previously reported pH-induced increase of developmental defects in the offspring of acid-exposed sperm (Pagano et al.: Teratogenesis Carcinogen Mutagen 5:113-121, 1985).

Animals

Effect of mercuric ion on attraction to light of artemia sp nauplii.

Living organisms exhibit a phototactic response which can be altered by certain environmental toxic chemical species. The analysis of photobehavior can help in elucidating environmental factors that influence photomotility reactions of the organisms. A method has been developed that measures the phototactic response of Artemia nauplii under the influence of mercuric ion (Hg2+) in synthetic seawater. The phototactic response of Artemia nauplii was manifested by movement of the organisms from a darkened half to lighted half of an experimental vessel containing synthetic seawater. The density as a function of time of Artemia nauplii is determined by removing aliquots from both light and dark sides and then plating on agar for counting under the dissecting microscope. Measurements consistently show a significant movement of nauplii to the lighted side within 45 min of the start of the experiments. The present investigation demonstrated that at concentrations as low as 0.010 mg HgCl2/liter there is an enhancement of phototactic effect on Artemia nauplii by mercuric ion as compared with control. The phototactic response of Artema nauplii is altered by mercuric ion in a dose-related manner, but the mechanism of this effect is presently unknown.

Animals

Effect of acute acrylonitrile exposure on metrazol induced seizures in the rat.

The effects of acute exposure to acrylonitrile (ACN), 10, 20, or 40 mg/kg by gavage, on the ability of metrazol (MTZ) to induce seizures was studied in adult, male Sprague-Dawley rats. The frequency of seizure occurrence and the frequency of a lethal seizure was greater when the high ACN dosage was given in combination with metrazol. This dosage of ACN was not lethal when given alone. Examination of brain tissue in these animals revealed no difference in cyanide levels when MTZ was combined with ACN. However, brain cytochrome c was significantly lower in animals given ACN+MTZ and brain cholinesterase was significantly higher. These results suggest that the enhanced lethality occurring in animals exposed to the combination of ACN+MTZ is not due to cyanide, a metabolic product of ACN, but rather to a potentiation of other effects of ACN perhaps involving cholinergic neurotransmission.

Acetylcholinesterase

The evaluation of mutagenicities of 19 structurally related aromatic amines and acetamides in Salmonella typhimurium TA98 and TA100.

19 aromatic amines were assayed for mutagenicity using Salmonella typhimurium strains TA98 and TA100 with and without the addition of S9 from Aroclor-1254-induced rat liver. These included: naphthalenes (1-amino-, 1-acetamido-, 2-amino-, 2-acetamido-, 1-amino-4-nitro- and 2-amino-1-nitro-), biphenyls (2-amino-, 2-acetamido-, 4-amino- and 4-acetamido-), fluorenes (2-amino- and 2-acetamido-), anthracenes (1-amino-, 1-acetamido-, 2-amino- and 2-acetamido-), 3-aminofluoranthene, 1-aminopyrene and 6-aminochrysene. None of the compounds were mutagenic when tested without S9. With S9, 15 of 19 were mutagenic for TA98 and 16 of the 19 were mutagenic for TA100. Overall, 2-aminoanthracene was the most potent mutagen. When compared to the parent amines, the respective acetamido derivatives were consistently less mutagenic.

Acetamides

Occupational exposure to formaldehyde in a medical center autopsy service.

The formaldehyde exposures occurring in the autopsy service of a medical complex were evaluated as part of a study to detect genetically harmful effects of chemical exposures. Determination of time-weighted average (TWA) exposures and characterization of the patterns of exposure experienced by individuals with different work responsibilities in this occupational setting were sought. Both general area and breathing zone samples were evaluated. Estimated weekly time-weighted average exposures for pathologists, residents and technicians were determined to be between 0.61 and 1.32 parts per million with little difference between work roles. While the averages were similar, the patterns of exposure of technicians and physicians were different. Technicians were exposed to a baseline level of formaldehyde for a prolonged period of time. In contrast, physicians were exposed for shorter times but experienced higher levels during specific tasks, particularly tissue-sectioning and examination. Evaluations of work procedures and environmental conditions in autopsy services are recommended to reduce personnel exposure to formaldehyde vapor.

Academic Medical Centers

Transient decrease of liver cytosolic glutathione S-transferase activities in rats given 1,2-dibromoethane or CCl4.

In vivo treatment of fasted male rats with 1,2-dibromoethane (DBE) (0.4 mmol/kg) or carbon tetrachloride (CCl4) (4 mmol/kg) was found to rapidly alter the activities of liver cytosolic and microsomal glutathione S-transferases. Microsomal activities towards chloro-2,4-dinitrobenzene (CDNB) were increased 2 h after either treatment. Cytosolic activities towards CDNB and 3,4-dichloronitrobenzene (DCNB), but not 1,2-epoxy-3-(p-nitrophenoxy)-propane (ENPP), were selectively and transiently decreased after either treatment. Time course studies in DBE animals indicated that the decrease in cytosolic activity was not evident until 2 h although liver glutathione (GSH) concentrations were diminished within 15 min. In contrast, in CCl4 animals the decrease in cytosolic activity was evident within 15 min and was not accompanied by diminished GSH concentrations. By 4 h, cytosolic activities had rebounded to control levels in both DBE and CCl4-treated animals. Kinetic studies of the enzyme in liver cytosol from animals 2 h after treatment with DBE or CCl4 indicated that both treatments decreased the apparent Vmax while neither treatment altered the apparent Km. This pattern of change allows exclusion of a simple competitive mechanism of enzyme inhibition, but cannot distinguish between reversible non-competitive inhibition and irreversible inhibition. It is possible that the observed decreases in the activities of the abundant cytosal enzyme are due to 'sacrificial' covalent linkages between the enzyme and reactive metabolites of DBE or CCl4.

Animals

Inactivation of poliovirus by chloramine-T.

Since concern has recently been expressed about the presence of genotoxic substances due to chlorination of water and wastewater, chloramine-T (CAT) is proposed as an alternative disinfectant to chlorine. The viricidal properties of chlorine and CAT were compared. Kinetics of inactivation of poliovirus type 2 by chlorine and CAT in chlorine demand-free water were investigated by using a kinetic apparatus. Inactivation of the virus by chlorine and CAT occurred in two steps. The initial linear part of the inactivation curve followed a pseudo-first-order reaction with the virus. An obvious dose-response relationship was demonstrated with CAT. The rate of inactivation of the virus by CAT was faster in acid medium than in alkaline medium. Inactivation kinetic studies were performed at different temperatures, and the kinetic, Arrhenius, and thermodynamic parameters were evaluated. The rate of inactivation of poliovirus type 2 by chlorine was faster than that by CAT under identical conditions. A mechanism for the viral inactivation in acid conditions was proposed which led to a rate equation consistent with the experimental results. The results indicate that CAT may be an effective viricide against poliovirus type 2 in an acid medium.

Chloramines

Correlation of the chemical structure of 4-nitroquinolines inactivating human cytomegalovirus and established in vivo carcinogenicity tests.

Inactivation of the infectivity of human cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) has been observed following exposure to 4-nitroquinoline 1-oxide (NQO) or its metabolite, 4-hydroxyaminoquinoline 1-oxide (HAQO). The present study of the specificity of the chemical structure of 4-nitroquinolines demonstrated that both the 4-nitro and 1-oxide groups were required for inactivation of virus infectivity. Reduction of the 4-nitro group to a 4-hydroxyamino group enhanced activity, while further reduction to an amino group resulted in loss of activity against virus infectivity. The capacity to inactivate virus was also lost by substitution of the pyridine ring for the quinoline nucleus of NQO. The relationship between the chemical structure and the ability to inactivate viruses studied here correlates well with earlier in vivo carcinogenicity studies of the same group of chemicals.

4-Nitroquinoline-1-oxide

Kinetics of uptake and biliary excretion of benzo(alpha)pyrene and mutagenic metabolites in isolated perfused rat liver.

An isolated liver perfusion system was used as a simplifying tool to study the metabolism and excretion of benzo(alpha)pyrene (BP) as a prototype carcinogen/mutagen. Phenobarbital (PB) was used to induce liver microsomal enzymes in Sprague-Dawley male rats prior to isolated liver perfusion. Control livers were run simultaneously using generally tritiated (G-3H)BP/BP as substrate in the perfusion medium. Both biliary excretion and liver weight were increased in the induced compared to control liver, but biliary flow when corrected for liver weight is statistically the same for both control and PB-induced livers. The excretion rat of radioactivity in the bile is always higher for PB-induced than for control liver (maximum radioactive excretion at 1 hr). There is a more rapid radioactivity removal in the liver perfusion medium for PB-induced than for control livers. Data are explained by increased metabolism of BP in induced liver leading to the presence of more polar metabolites undergoing preferential biliary excretion than in the control liver. Results support in vivo experimental data. Extracts from liver and bile were tested for microbial mutagenicity by the Ames test (TA 100) after TLC separation. The control liver shows virtually no mutagenicity in bile, only in TLC fractions from the liver. The PB-induced liver shows significant mutagenicity in several TLC fractions in both bile and liver. The net effect of induction is to produce more mutagenic metabolites of BP, excreted in the bile, and presenting a significant exposure of carcinogens/mutagens, and consequent hazard to man.

Animals

High pressure liquid chromatographic separation of two major toxic compounds from Gymnodinium breve davis.

Cultured Gymnodinium breve cells were extracted in acidified ether and fractionated by a new, convenient procedure utilizing thin layer chromatography or elution dry column chromatography. The most toxic fraction was further separated either directly by analytical high pressure liquid chromatography (HPLC) or in subsequent work by preparative, followed by analytical HPLC. Two toxic compounds, designated T46 and T47, were isolated; purity of each was demonstrated by rechromatography in analytical HPLC with both adsorptive and reverse phase packings. Both the single pass and recycle modes of operation were used with two detector systems in each to demonstrate a single entity. UV, fluorescence, and stability data differentiated these compounds from previously described, less toxic components from G. breve.

Animals