A method for studying the mutagenicity of some gaseous compounds in <i>salmonella typhimurium</i>

Victorin, Katarina; Ståhlberg, Margareta

doi:10.1002/em.2850110108

Cited by 42 publications

(14 citation statements)

References 44 publications

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“…EtO is a tobacco smoke toxicant and was selected for use in this study as it is a direct acting genotoxic agent with known mutagenic properties in vitro and in vivo [Victorin and Stahlberg, ; Agurell et al, ; Thier and Bolt, ]. A 2‐year exposure to EtO was found to preferentially induce GGT → GTT mutations at codon 12 of K‐ ras in the lung tumours of B6C3F1 mice [Hong et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…EtO has previously been shown to be highly mutagenic in Salmonella typhimurium strain TA100 when tested at concentrations of 1–200 ppm in a continuous flow system over a 6 hr exposure period, both in the presence and absence of a rat S9 metabolic activation system [Victorin and Stahlberg, ]. Further evidence of a mutagenic effect of EtO in the Ames assay was detailed in a study where Salmonella typhimurium strains TA100 and TA1535 were exposed to EtO for 4 hr in suspension culture, plated on minimal agar and cultured for 48 hr before scoring of the resulting colonies.…”

Section: Discussionmentioning

confidence: 99%

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Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants

Breheny

Cunningham

Kilford

et al. 2014

Environ and Mol Mutagen

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Tobacco smoke is a complex mixture of over 6,000 individual chemical constituents. Approximately 150 of these have been identified as 'tobacco smoke toxicants' due to their known toxicological effects. A number of these toxicants are present in the gaseous phase of tobacco smoke. This presents a technical challenge when assessing the toxicological effects of these chemicals in vitro. We have adapted a commercially available tobacco smoke exposure system to enable the assessment of the contribution of individual smoke toxicants to the overall toxicological effects of whole mainstream cigarette smoke (WS). Here we present a description of the exposure system and the methodology used. We use the example of a gaseous tobacco smoke toxicant, ethylene oxide (EtO), a Group 1 IARC carcinogen and known mutagen, to illustrate how this methodology can be applied to the assessment of genotoxicity of gaseous chemicals in the context of WS. In the present study we found that EtO was positive in Salmonella typhimurium strain YG1042, a strain that is sensitive to tobacco smoke. However, EtO did not increase the mutagenicity of the WS mixture when it was added at greatly higher concentrations than those found typically in WS. The findings presented here demonstrate the suitability of this exposure system for the assessment of the mutagenic potential of gases in vitro. Whilst we have focused on tobacco smoke toxicants, this system has broad application potential in studying the biological effects of exposure to a wide range of gaseous compounds that are present within complex aerosol mixtures. Environ. Mol. Mutagen. 55:662-672,

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants

Breheny

Cunningham

Kilford

et al. 2014

Environ and Mol Mutagen

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“…NO 2 is very reactive and thought to be toxic to microorganism. It has been reported that NO 2 caused chromosome aberrations in cultured Chinese hamster (Tsuda et al, 1981) and mutations in Salmonella typhimurium (Victorin and Stahlberg, 1988). One group (Kosaka et al, 1986) bubbled a NO 2 gas into 5 mL fractions for 30 min at a flowrate of 0.1 L/min and found wild type E. coli was resistant to 90 ppm NO 2 .…”

Section: The Effect Of Gas Impuritiesmentioning

confidence: 99%

Process Design for the Biocatalysis of Value-Added Chemicals from Carbon Dioxide

Eiteman¹

2007

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ABSTRACT:This report describes results toward developing a process to sequester CO 2 centered on the enzymes PEP carboxylase and pyruvate carboxylase. The process involves the use of bacteria to convert CO 2 and glucose as a co-substrate and generates succinic acid as a commodity chemical product.The study reports on strain development and process development. In the area of strain development, knockouts in genes which divert carbon from the enzymatic steps involved in CO 2 consumption were completed, and were shown not to affect significantly the rate of CO2 sequestration and succinic acid generation. Furthermore, the pyc gene encoding for pyruvate carboxylase proved to be unstable when integrated onto the chromosome.In the area of process development, an optimal medium, pH and base counterion were obtained, leading to a sequestration rate as great as 800 mg/Lh. Detailed studies of gas phase composition demonstrated that CO2 composition has a significant affect on CO2 sequestration, while the presence of "toxic" compounds in the gas, including NO 2 , CO and SO 2 did not have a detrimental effect on sequestration. Some results on prolonging the rate of sequestration indicate that enzyme activities decrease with time, suggesting methods to prolong enzyme activity may benefit the overall process.

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“…In spite of the formation of its carcinogenic metabolite EO, ET was found to be negative in mutagenicity studies in vitro and in vivo in rodents (Victorin and Ståhlberg, 1988; Walker et al , 2000) and in a long-term carcinogenicity study in rats (Hamm et al , 1984). The negative outcome of the carcinogenicity study was expected from toxicokinetic studies with ET and EO in rats and from studies on hemoglobin adducts in rats and mice.…”

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confidence: 99%

Kinetics of Ethylene and Ethylene Oxide in Subcellular Fractions of Lungs and Livers of Male B6C3F1 Mice and Male Fischer 344 Rats and of Human Livers

Csanády

Kessler

et al. 2011

Toxicological Sciences

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Ethylene (ET) is metabolized in mammals to the carcinogenic ethylene oxide (EO). Although both gases are of high industrial relevance, only limited data exist on the toxicokinetics of ET in mice and of EO in humans. Metabolism of ET is related to cytochrome P450-dependent mono-oxygenase (CYP) and of EO to epoxide hydrolase (EH) and glutathione S-transferase (GST). Kinetics of ET metabolism to EO and of elimination of EO were investigated in headspace vessels containing incubations of subcellular fractions of mouse, rat, or human liver or of mouse or rat lung. CYP-associated metabolism of ET and GST-related metabolism of EO were found in microsomes and cytosol, respectively, of each species. EH-related metabolism of EO was not detectable in hepatic microsomes of rats and mice but obeyed saturation kinetics in hepatic microsomes of humans. In ET-exposed liver microsomes, metabolism of ET to EO followed Michaelis-Menten-like kinetics. Mean values of Vmax [nmol/(min·mg protein)] and of the apparent Michaelis constant (Km [mmol/l ET in microsomal suspension]) were 0.567 and 0.0093 (mouse), 0.401 and 0.031 (rat), and 0.219 and 0.013 (human). In lung microsomes, Vmax values were 0.073 (mouse) and 0.055 (rat). During ET exposure, the rate of EO production decreased rapidly. By modeling a suicide inhibition mechanism, rate constants for CYP-mediated catalysis and CYP inactivation were estimated. In liver cytosol, mean GST activities to EO expressed as Vmax/Km [μl/(min·mg protein)] were 27.90 (mouse), 5.30 (rat), and 1.14 (human). The parameters are most relevant for reducing uncertainties in the risk assessment of ET and EO.

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A method for studying the mutagenicity of some gaseous compounds in salmonella typhimurium

Cited by 42 publications

References 44 publications

Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants

Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants

Process Design for the Biocatalysis of Value-Added Chemicals from Carbon Dioxide

Kinetics of Ethylene and Ethylene Oxide in Subcellular Fractions of Lungs and Livers of Male B6C3F1 Mice and Male Fischer 344 Rats and of Human Livers

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