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At least 1,207 records · Page 67Linked to original sources
PubMed1999

In vitro cytocompatibility of radio-opacifiers used in ureteral endoprosthesis.

Ureteral endoprostheses are urinary catheters made of polymeric biomaterials made radio-opaque through the addition of X-ray absorbing additives such as barium, bismuth, tantale or tungsten. The aim of this work was to study the in vitro toxicity of solutions of these radio-opacifiers using two cell culture models. Primary-cultures of human urothelial cells (HUC) arising from normal adult urinary tract and permanent urothelial cell line were used. Solutions at different dilutions were placed into the wells containing monolayers of confluent cells. After 24 h incubation period, the solutions were removed and cell viability and cell metabolic activity tests were performed (Neutral Red assay and MTT assay). At a concentration lower than 1 mg l(-1) the different radio-opacifiers used showed no toxicity. From 1 to 3 mg l(-1) one can note a significant dose-dependent decrease of cell metabolic activity of solely HUC for barium chloride. At 3 mg l(-1) one can note a significant deleterious effect on HUC metabolic activity, with bismuth and tantale. For tungsten, there is no deleterious effect, but on the contrary a significant increase in HUC metabolic activity at a 0.5 mg l(-1) concentration. None of the solutions did provoke alterations in HUC viability for concentrations less than 3 mg l(-1). Interestingly, for permanent cell line one can note a solely significant decrease of cell viability at 3 mg l(-1) for tantale. All the other tested salts on permanent cell line were not significantly different from controls for cell viability as well as cell metabolic activity. HUC culture model may be of relevance for the screening of radio-opacifiers intended for ureteral endoprostheses.

Adult↗
PubMed2000

Identification of the subcellular localization of daunorubicin in multidrug-resistant K562 cell line.

We examined the subcellular distribution of daunorubicin (DNR) in resistant K562 cell line which overexpress the P-glycoprotein by confocal laser scanning microscopy. Three fluorescent probes - Rhodamine123, neutral red, NBD-ceramide, which stain the mitochondria, lysosomes, Golgi apparatus respectively, were used to identify the nature of the subcellular compartment sequestering daunorubicin. In sensitive k562 cell line, nuclear and cytoplasmic DNR fluorescence was intense and diffuse. In contrast, resistant K562 cell line showed a different DNR distribution. A bright fluorescence signal was located in the perinuclear region and peripheral plasma, the nucleus and other cytoplasmic region appear as empty, as suggested by the distribution of fluorescent probe Rhodamine123 specifically for mitochondria. Verapamil, an effective resistance modulator in P-glycoprotein MDR cells, restored the DNR distribution closer to that in the parent cells. Golgic inhibitor brefeldin A and lysosomotropic agent chloroquine had little effect on drug sequestration. Our studies demonstrate that daunorubicin may be sequestered in mitochondrial compartment in the resistant cells and P-glycoprotein plays an important role on mediating DNR transport.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Cytotoxic effects of two antimolting insecticides in mammalian CHO-K1 cells.

Cytotoxicity of two insect growth regulators, diflubenzuron, a benzoylphenylurea derivative that inhibits the synthesis of new chitin in target organisms, and pyriproxyfen, an insect juvenile hormone analogue, were tested on CHO-K1 cultures, using the neutral red incorporation assay. Both compounds displayed cytotoxic effects that rise with time exposure. The presence of either fetal calf serum or bovine serum albumin diminished significantly the cytotoxicity of both compounds, thus pointing to a strong protein binding. In addition, extensive metabolization with rat liver submitochondrial fraction gave rise to metabolites less toxic than the parent compounds, implying the relative safety of both diflubenzuron and pyriproxyfen in mammals.

Animals↗
PubMed2003

The influence of exposure history to lead on the lysosomal response in Eisenia fetida (Oligochaeta).

In this study groups of the epigeic earthworm species Eisenia fetida were exposed experimentally for different periods to sublethal concentrations of Pb(NO3)2. The lysosomal membrane fragility response of coelomocytes was used as a biomarker to explore the cytotoxity of Pb by determining the neutral red retention times (NRRTs) and correlating them with different body loads of Pb. Previously unexposed worms exposed to different low concentrations of Pb(NO3)2 for 4 weeks demonstrated a clear dose-response relationship between NRRTs and body burdens of Pb. The NRRTs of growing worms with a previous (ancestral) exposure history, exposed to an elevated concentration of Pb and measured over time, fluctuated around a mean of 41 min and no dose-related relationship could be demonstrated. Worms with a long-term history of exposure to Pb of more than 36 months had a mean body burden of 177.5 +/- 61.5 mg/kg Pb and a mean NRRT of 57.8 +/- 3.1 min, which was significantly lower than that of uncontaminated, control worms with a mean time of 61.9 +/- 3.4 min and a mean body burden of 86.3 +/- 47.2 mg/kg. No significant differences were found between weight changes of "clean" and preexposed worms when they were experimentally exposed to sublethal concentrations of Pb. This study provided evidence that the lysosomal biomarker response for Pb may not persist at the same level in worms with a previous history of Pb exposure, possibly making it less sensitive as a tool for comparing responses to Pb in field populations of earthworms.

Animals↗
PubMed2004

Evaluating the toxicity of Triton X-100 to protozoan, fish, and mammalian cells using fluorescent dyes as indicators of cell viability.

Three viability assays using fluorescent dyes effectively detected a loss of viability in cultures of three mammalian cell lines (H4IIE, Caco2, and HepG-2), two fish cell lines (RTgill-W1 and RTL-W1), and a ciliated protozoan, Tetrahymena thermophila, after exposure to Triton X-100, used as a model toxicant. The dyes were Alamar Blue (AB), neutral red (NR), and propidium iodide, which respectively monitored energy metabolism, lysosomal activity, and membrane integrity. A fourth fluorescent dye, 5-carboxyfluorescein diacetate acetoxymethyl ester, was problematic. For 2-h Triton X-100 exposures, mammalian cell lines were as susceptible as piscine cell lines, whereas T. thermophila was approximately twofold less sensitive as detected with AB and NR. Despite being less sensitive, cytotoxicity tests on T. thermophila could be done in spring water, which means that unlike animal cells they could be directly exposed to most industrial effluents without osmolality adjustments. Therefore, T. thermophila could be a useful complement to animal cells as alternatives to fish in toxicity testing.

Animal Testing Alternatives↗
PubMed2002

Development of a novel influenza A antiviral assay.

Traditional methods used to monitor influenza infection typically require 2-5 days to perform, prompting a need for more rapid and quantitative methods for monitoring viral infection in 96-well formats. Such assays would find application in high-throughput screening for novel antiviral agents. A new method, based on branched DNA (bDNA) technology, is described for the specific detection of negative strand RNA of influenza A strains using a set of oligonucleotides designed for the A/PR/8/34 nucleoprotein (NP) transcript. By detecting the genomic strand, this signal amplification assay is appropriate for monitoring the kinetics of viral replication. Assay performance was monitored following infection of MDCK cells. The assay exhibited high reproducibility, good sensitivity over a range of multiplicity of infection and has a lower limit of detection of approximately 5 x 10 (5) RNA copies. Designed to quantitate the H1N1 strain A/PR/8/34, the assay also detects other influenza A subtypes, but not the evolutionarily more distant strain B/Yamagata/16/88. Validation as an antiviral assay was demonstrated with two influenza antivirals, zanamivir and rimantadine. The EC(50) values calculated following bDNA detection for zanamivir (265 nM) and rimantadine (9.4 microg/ml) in A/PR/8/34 infection correlate closely to data previously reported from visual CPE determinations, neutral red dye uptake and plaque assays, respectively. The advantages over the more time-consuming traditional assays suggest that the influenza bDNA assay is applicable to rapid screening of compound collections for antiviral activity.

Animals↗
PubMed2002

Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds.

Methods have been developed previously for rapid evaluation of compounds for antiviral activity in 96-well microplates, which include visual quantitation of antiviral activity based upon inhibition of virus-induced cytopathic effect (CPE) or by less subjective colorimetric or fluorometric means. In the present studies we compared a number of colorimetric (crystal violet, MTT [3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide], and neutral red) and fluorometric (Alamar Blue, bisbenzimide [Hoechst 33258], fluorescein diacetate, and rhodamine 6G) methods to visual scoring of antiviral activity in influenza A virus infections in Madin Darby canine kidney (MDCK) cells. Toxicity determinations using these same methods were also made for anti-influenza inhibitors and other compounds known to inhibit cell proliferation. Against influenza A/Texas/36/91 (H1N1) and A/Sydney/05/97 (H3N2) viruses, visual scoring and dye or stain methods produced results that were not significantly different from each other in deriving 50% virus-inhibitory concentrations (EC(50) values) for six anti-influenza compounds (amantadine, rimantadine, ribavirin, RWJ-270201 [BCX-1812], oseltamivir carboxylate, and zanamivir), with the exception of Alamar Blue which quantified lower EC(50) values than expected. In uninfected replicating cells, the visual and Alamar Blue methods underestimated the 50% cytotoxic concentrations (IC(50) values) of ribavirin, 1-beta-D-arabinofuranosylcytosine, and 6-azauridine, but more accurately assessed the toxicities of amantadine, rimantadine, and cycloheximide. Visual scoring, coupled with the use of one of these dyes or stains except Alamar Blue, can be used to accurately and rapidly quantify the anti-influenza virus activities and toxicities of potential new influenza virus inhibitors. These methods should also be applicable to evaluating antiviral effects against other lytic virus infections.

Animals↗
PubMed2002

Identification of active antiviral compounds against a New York isolate of West Nile virus.

The recent West Nile virus (WNV) outbreak in the United States has increased the need to identify effective therapies for this disease. A chemotherapeutic approach may be a reasonable strategy because the virus infection is typically not chronic and antiviral drugs have been identified to be effective in vitro against other flaviviruses. A panel of 34 substances was tested against infection of a recent New York isolate of WNV in Vero cells and active compounds were also evaluated in MA-104 cells. Some of these compounds were also evaluated in Vero cells against the 1937 Uganda isolate of the WNV. Six compounds were identified to be effective against virus-induced CPE with 50% effective concentrations (EC50) less than 10 microg/ml and with a selectivity index (SI) of greater than 10. Known inhibitors of orotidine monophosphate decarboxylase and inosine monophosphate dehydrogenase involved in the synthesis of GTP, UTP, and TTP were most effective. The compounds 6-azauridine, 6-azauridine triacetate, cyclopententylcytosine (CPE-C), mycophenolic acid and pyrazofurin appeared to have the greatest activities against the New York isolate, followed by 2-thio-6-azauridine. Anti-WNV activity of 6-azauridine was confirmed by virus yield reduction assay when the assay was performed 2 days after initial infection in Vero cells. The neutral red assay mean EC50 of ribavirin was only 106 microg/ml with a mean SI of 9.4 against the New York isolate and only slightly more effective against the Uganda isolate. There were some differences in the drug sensitivities of the New York and Uganda isolates, but when comparisons were made by categorizing drugs according to their modes of action, similarities of activities between the two isolates were identified.

Amides↗
PubMed1997

Potent inhibition of respiratory syncytial virus by polyoxometalates of several structural classes.

A series of polyoxometalates (POM) were synthesized and evaluated for anti-respiratory syncytial virus (RSV) activity. POM containing zirconium, tungsten, silicon, platinum, niobium or germanium of a variety of structural types have been evaluated. Sixteen of the compounds had very striking anti-RSV activity against a clinical isolate, Utah 89, with median effective concentration (EC50) values < or = 3 microM and selective indices > 80 as determined by viral cytopathic inhibition effect, neutral red uptake and virus yield reduction assays. The EC50 values for all three assays correlated very well (Pearson correlation coefficients > 0.90). POM containing sodium cations were totally inactive. Germanium-, niobium-, tin- and zirconium-containing compounds were found to be highly potent and selective. The antiviral activity was not cell line-dependent. The median cytotoxic concentration (IC50) values were generally greater than 100 microM. The compounds were also comparably active against a known laboratory RSV strain, A2, as well as other RSV strains. To detect any virus strain-specific inhibitory activity, seven POM were tested against other RSV strains; all were nearly equally inhibitory to the human virus strains, suggesting no strain specificity. Timing studies suggested that these compounds were most inhibitory during virus adsorption and penetration, although RSV was still significantly inhibited when the compound was added 3 h post-infection; which is considered well into the eclipse period. These data suggest that these potent, non-toxic compounds should be further studied as potential chemotherapeutic agents for treating RSV infections.

Animals↗
PubMed1998

Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor.

The carbocyclic transition state sialic acid analog GS4071 ([3R,4R,5S]-4-acetamido-5-amino-3-[1-ethylpropoxy]-1-cyclohexane-1 -carboxylic acid), a potent influenza virus neuraminidase inhibitor, was highly inhibitory to influenza A/NWS/33 (H1N1), A/Victoria/3/75 (H3N2), A/Shangdong/09/93 (H3N2) and B/Hong Kong/5/72 viruses in Madin Darby canine kidney (MDCK) cells. The 50% effective concentrations in these experiments ranged from 1.8 to 59.5 microM, with no cytotoxicity evident at 1000 microM, using inhibition of viral cytopathic effect determined visually and by neutral red dye uptake. The ethyl ester prodrug of GS4071, GS4104, administered by oral gavage (p.o.), had significant inhibitory effects on infections in mice induced by these viruses. Antiviral effects were seen as prevention of death, increase in mean day to death, inhibition of decline of arterial oxygen saturation, lessened lung consolidation and inhibition of infectious virus recovered from the lungs. No toxicity was seen in dosages up to 100 mg/kg/day (highest evaluated). Comparison experiments run versus the influenza A (H1N1) virus-induced infection using GS4104, GS4071 and the neuraminidase inhibitor zanamivir (GG167, 4-guanidino-Neu5Ac2en), all administered p.o., indicated a 10-fold or greater potency for inhibiting the infection by GS4104. The minimum effective dosage for GS4104 was 0.1 mg/kg/day, with the compound administered twice daily for 5 days beginning 4 h pre-virus exposure. Oral therapy with GS4104 could be delayed from 48 to at least 60 h after exposure of mice to influenza A (H1N1) virus and still render a significant antiviral effect, the time of delay being dependent on the viral challenge dose. Intranasal instillation of GS4071 and GG167 to mice infected with influenza virus was highly inhibitory to the infection, the minimum effective dosages to significantly prevent death being 0.01 mg/kg/day for GS4071 and 0.1 mg/kg/day for GG167. Caging of infected mice treated with 10 mg/kg/day of GS4104 with infected saline-treated animals did not transfer any influenza-inhibitory effect to the latter animals. These data provide strong evidence of the potential of orally administered GS4104 for treatment of influenza A and B virus infections in humans.

Acetamides↗
PubMed1998

Antiviral activity of Viracea against acyclovir susceptible and acyclovir resistant strains of herpes simplex virus.

Viracea, a topical microbicide, is a blend of benzalkonium chloride and phytochemicals derived from Echinacea purpurea and is a proprietary formula from Destiny BioMediX Corp. Viracea was tested against 40 strains of herpes simplex virus (HSV): 15 strains (five HSV-1 and ten HSV-2) were resistant to acyclovir (ACV-R) and 25 strains (13 HSV-1 and 12 HSV-2) were susceptible to ACV (ACV-S). The median ED50 of Viracea for the five ACV-R strains of HSV-1 was a 1:100 dilution of the drug with a range of 1:50-1:400. The median ED50 of Viracea for the ten ACV-R strains of HSV-2 was 1:200 with a range of 1:50-1:3200. For the ACV-S strains of HSV-1 and HSV-2, the median ED50 of Viracea was 1:100 and 1:200, respectively. The cytotoxicity of Viracea was evaluated in a standard neutral red dye uptake assay in human foreskin fibroblasts. The cytotoxicity of Viracea approached only 50% at the highest concentration of the drug tested, a 1:2 dilution, indicating that Viracea is non-toxic in this cell cytotoxicity assay. Although the active component(s) in Viracea that has anti-HSV activity is not known, it appears that this extract has good antiviral activity against both ACV resistant and ACV susceptible strains of HSV-1 and HSV-2.

Acyclovir↗
PubMed1999

2-5A-DNA conjugate inhibition of respiratory syncytial virus replication: effects of oligonucleotide structure modifications and RNA target site selection.

To define more fully the conditions for 2-5A-antisense inhibition of respiratory syncytial virus (RSV), relationships between 2-5A antisense oligonucleotide structure and the choice of RNA target sites to inhibition of RSV replication have been explored. The lead 2-5A-antisense chimera for this study was the previously reported NIH8281 that targets the RSV M2 RNA. We have confirmed and extended the earlier study by showing that NIH8281 inhibited RSV strain A2 replication in a variety of antiviral assays, including virus yield reduction assays performed in monkey (EC90 = 0.02 microM) and human cells (EC90 = microM). This 2-5A-antisense chimera also inhibited other A strains, B strains and bovine RSV in cytopathic effect inhibition and Neutral Red Assays (EC50 values = 0.1-1.6 microM). The 2'-O-methylation modification of NIH8281 to increase affinity for the complementary RNA and provide nuclease resistance, the introduction of phosphothioate groups in the antisense backbone to enhance resistance to exo- and endonucleases, and the addition of cholesterol to the 3'-terminus of the antisense oligonucleotide to increase cellular uptake, all resulted in loss of activity. Of the antisense chimeras targeting other RSV mRNAs (NS1, NS2, P, M. G, F, and L), only those complementary to L mRNA were inhibitory. These results suggest that lower abundance mRNAs may be the best targets for 2-5A-antisense; moreover, the active 2-5A antisense chimeras in this study may serve as useful guides for the development of compounds with improved stability, uptake and anti-RSV activity.

Adenine Nucleotides↗
PubMed2000

Total oxyradical scavenging capacity (TOSC) in polluted and translocated mussels: a predictive biomarker of oxidative stress.

Several classes of environmental pollutants are known to enhance the intracellular formation of reactive oxygen species in marine invertebrates with different consequences on their antioxidant system. Despite variations in the endogenous levels of antioxidants may reveal biological effects induced by pollutants, the overall efficiency of antioxidant system is not evaluated from such data. The total oxyradical scavenging capacity (TOSC) assay measures the biological resistance to various kinds of oxyradicals, thus providing useful indications to predict oxyradical-mediated adverse effects on the physiological condition of the organisms. In the present work, the capability to neutralize three potent cellular oxidants (peroxyl radicals, hydroxyl radicals and peroxynitrite) was compared in two natural populations of mussels from a clean and a metal polluted area, respectively, and in control organisms translocated for 8 weeks to the contaminated site. Within each group of mussels, the relative efficiency towards the various forms of oxyradicals, showed peroxyl radicals and hydroxyl radicals as the less and the most difficult species, respectively, to neutralize by cellular antioxidants. When the two populations were compared, polluted organisms revealed a significantly higher susceptibility to oxidative stress as indicated by their lower TOSC values. A significant reduction of antioxidant capacity was observed also in translocated organisms where only a moderate recovery was evident at the longer exposure time. Separation of soluble antioxidants from the protein fraction, suggested a greater depletion of low molecular weight molecules during the first phase of exposure to pollutants. The pollutant-induced impairment of antioxidant capability precludes the appearance of oxyradical toxicity. In the present study a high correlation was obtained between reduced TOSC values and lower Neutral Red retention time in lysosomal compartment of circulating haemocytes. The TOSC towards different forms of oxyradicals is confirmed an useful biomarker with predictive validity at the organism level.

Journal Article↗
PubMed2006

[Role of conditioning medium cytotoxicity. An example with an intraocular lens preloaded in injector].

INTRODUCTION: Following material vigilance cases encountered with the hydrophilic acrylic intraocular lens, ACR6D SE preloaded in the Premier shooter, we studied the cytotoxicity of the intraocular lens and its conditioning to identify the cytotoxic element. We proposed medical device modification to improve its biocompatibility. MATERIALS AND METHODS: Biocompatibility-cytotoxicity assays were carried out according to ISO 10993-5 recommendations. Tests were performed on the SRA 01/04 human lens epithelial cell line. Neutral red, Hoechst 33342, and YO-PRO-1 fluorescent probes were used to assess membrane integrity, total DNA, and membrane fluidity, respectively. Materials samples were prepared in culture medium according to the ISO 10993-5 elution procedure. Pure saline solutions and conditioning liquids were tested directly on cells. RESULTS: The intraocular lens and injector were not cytotoxic. Conditioning liquids induced membrane fluidity perturbation characteristic of apoptosis. Tests performed on new versions of the medical device identified a better adapted conditioning liquid. CONCLUSION: The results suggest that the cytotoxicity of the conditioning liquid could explain the postoperative complication rate. When we changed the conditioning liquid with sterile irrigating solution (i.e., rich divalent cation marine solution), we eliminated cellular stress. Fluorescent probes are well adapted to assess medical device biocompatibility-cytotoxicity.

Biocompatible Materials↗
PubMed2003

Effect of beta-amyloid on endothelial cells: lack of direct toxicity, enhancement of MTT-induced cell death and intracellular accumulation.

Several cerebrovascular alterations have been described in Alzheimer's disease (AD) including an accumulation of beta-amyloid (betaA) on the vascular walls in the brain. To investigate the potential toxic activity of betaA on endothelial cells (EC), two endothelial murine cell lines derived from heart and brain were exposed to betaA1-42 and the biologically active fragment betaA25-35 in the range from 5nM to 50 microM. In a low concentration range (50 nM to 2.5 microM) both peptides significantly reduced the 3-(4,5-dimethylthiazol-2y1)-2-5-diphenyltetrazolium bromide (MTT) signal in the endothelial cell lines exposed for 24h. However, microscopic examination, lactate dehydrogenase (LDH) release determination and Neutral Red assay did not confirm any toxic effect associated with inhibition of MTT formazan reduction. The effect on MTT was not susceptible to anti-oxidant treatment and did not increase the sensitivity to oxidative stress. However, when the EC were exposed to betaA and MTT for 1h, cell viability, determined by LDH release, was strongly reduced, while in normal conditions MTT-induced cell death only after 2h. An inhibitor of lysosomal ATPase activity, bafilomycin A1, completely antagonized this effect. The morphological examination showed that the functional activation by betaA in EC enhanced the production of MTT formazan crystals. To verify the accumulation of betaA in the lysosomal compartment we analyzed the subcellular distribution of betaA1-42 at different exposure times of EC to the peptide. The peptide was found in several organelles and was absent in the cytoplasmic compartment; co-treatment with bafilomycin A1 did not reduce the intracellular presence of betaA1-42. In our condition, the exposure of EC to betaA induced an intracellular accumulation of the peptide and a vasoactive effect that did not appear associated with direct toxic activity.

Amyloid beta-Peptides↗
PubMed2001

Synthesis, antimycobacterial activities and cytotoxicity on V79 of 3-[4'-Y-(1,1'-biphenyl)-4-yl]-N,N-dimethyl-3-(4-X-phenyl)-2-propen-1-amine derivatives.

The derivatives of 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine (5a-m) were synthesised through a Friedel-Crafts acylation followed by Wittig reaction. The effects of the compounds on standard strains of Mycobacterium sp. (ATCC) and M. tuberculosis isolated from clinical specimens were evaluated. Also the toxicity was determined on V79 cells line using neutral red uptake (NRU), nucleic acid content (NAC) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction to measure the cellular viability.

Alkenes↗
PubMed2002

Evaluation of the potential effects of ingredients added to cigarettes. Part 1: cigarette design, testing approach, and review of results.

A testing program was designed to evaluate the potential effects of 333 ingredients added to typical commercial blended test cigarettes on selected biological and chemical endpoints. Ingredients were incorporated into the test cigarettes as they are normally used in the manufacturing process. The studies performed included a bacterial mutagenicity screen (Ames assay), a mammalian cell cytotoxicity assay (neutral red uptake), determination of smoke chemical constituents, and a 90-day nose-only smoke inhalation study in rats. Three pairs of test cigarettes were produced, each containing one of three different groups of ingredients. In each pair, one of the cigarettes contained the normal approximate use level of the ingredients (low-level) and the other a 1.5-3 multiple of the normal use level (high-level). Analysis of the test cigarettes for selected ingredients or markers indicated that the target application rates were achieved and that the cigarettes had been manufactured as intended. Evaluation of cigarette performance indicated that the addition of the ingredients at high levels did not significantly alter the burning characteristics of the test cigarettes. Specific details of the individual studies conducted as part of an ingredient evaluation program are discussed in Parts 2-4 of this publication series (Food and Chemical Toxicology, 2002, 40, 93-104; Food and Chemical Toxicology, 2002, 40, 105-111; Food and Chemical Toxicology, 2002, 40, 113-131). The results of the smoke chemistry studies indicated a reduction in the majority of the smoke constituents and a few isolated instances of increases when compared to the control cigarettes. These smoke chemistry changes, while statistically significant, were not supported by any significant alteration in the biological effects of cigarette smoke normally seen with the bacterial mutagenicity assay, cytotoxicity assay or subchronic inhalation study. Based on the results of these studies, it can be concluded that these ingredients added to tobacco do not add significantly to the overall toxicity of cigarettes.

Animals↗
PubMed1999

Comparison of the cytotoxic and mutagenic potential of liquid smoke food flavourings, cigarette smoke condensate and wood smoke condensate.

Although products of pyrolysis are often cytotoxic and mutagenic, the relationship between the type of material pyrolysed and the toxicity of the resulting pyrolysis products is poorly understood. The objective of this study was to evaluate and compare the cytotoxicity and mutagenicity of several types of common pyrolysis products. The cytotoxicity and mutagenicity of these products were assessed by using neutral red uptake and Ames mutagenicity assays, respectively. The biological activities of four liquid smoke food flavourings (LSF) were compared with two other pyrolysis-derived materials; cigarette smoke condensate (CSC) and a wood smoke condensate (WSC). Results indicated all of the mixtures exhibited a concentration-dependent cytotoxic response. The CSC and WSC were less cytotoxic than three of the LSFs, but more cytotoxic than one of the brands. The CSC was mutagenic in two Salmonella strains; however, none of the LSFs or WSC was mutagenic using TA98, and only three of the LSFs were positive with TA100. The six pyrolysis-derived materials evaluated in this study showed differing patterns and magnitudes of cytotoxicity and mutagenicity. These results indicate that the cytotoxicity and mutagenicity of complex mixtures derived from pyrolysis products are affected by the type of material pyrolysed and/or the method used to prepare the mixture. The cytotoxic potential of some commercial smoke flavourings is greater than cigarette smoke condensate and several of the food flavourings are mutagenic in one Salmonella strain.

Animals↗