Evaluation of Two Derivatization Reagents for the Determination by LC-MS/MS of Ammonia in Cigarette Mainstream Smoke

Mottier, Nicolas; Jeanneret, Florent

doi:10.1021/jf103772c

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…4d ). Because the urea cycle mainly functions to prevent accumulation of toxic ammonia by converting excess nitrogen into ornithine and urea, we quantified 15 N-ammonia levels derived from 15 N-glutamine, following its chemical derivatization with dansyl chloride 23 . Consistent with an increase in nitrogen levels in obesity-associated PDA, we found a significant accumulation of 15 N-ammonia in tumors of the obese, the levels of which tended to further increase upon ARG2 knockdown ( P ≤ 0.05, one-way ANOVA followed by Tukey test, Fig.…”

Section: Resultsmentioning

confidence: 99%

Critical role for arginase 2 in obesity-associated pancreatic cancer

et al. 2017

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Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA. In vivo infusion of 15N-glutamine in obese mouse models of PDA demonstrates enhanced nitrogen flux into the urea cycle and infusion of 15N-arginine shows that Arg2 loss causes significant ammonia accumulation that results from the shunting of arginine catabolism into alternative nitrogen repositories. Furthermore, analysis of PDA patient tumors indicates that ARG2 levels correlate with body mass index (BMI). The specific dependency of PDA on ARG2 rather than the principal hepatic enzyme ARG1 opens a therapeutic window for obesity-associated pancreatic cancer.

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Section: Resultsmentioning

confidence: 99%

Critical role for arginase 2 in obesity-associated pancreatic cancer

et al. 2017

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“…The Cambridge filter pad does not trap all ammonia in mainstream smoke, as ammonia is present in both the particulate and gas phase. Efforts to trap gas phase ammonia usually involve a series of impingers with an acidic trapping solution [ 22 – 24 ]. Impingers are costly, impede sample throughput and produce large amounts of chemical waste.…”

Section: Resultsmentioning

confidence: 99%

Method for the Determination of Ammonia in Mainstream Cigarette Smoke Using Ion Chromatography

et al. 2016

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Ammonia in mainstream smoke is present in both the particulate and vapor phases. The presence of ammonia in the cigarette filler material and smoke is of significance because of the potential role ammonia could have in raising the “smoke pH.” An increased smoke pH could shift a fraction of total nicotine to free-base nicotine, which is reportedly more rapidly absorbed by the smoker. Methods measuring ammonia in smoke typically employ acid filled impingers to trap the smoke. We developed a fast, reliable method to measure ammonia in mainstream smoke without the use of costly and time consuming impingers to examine differences in ammonia delivery. The method uses both a Cambridge filter pad and a Tedlar bag to capture particulate and vapor phases of the smoke. We quantified ammonia levels in the mainstream smoke of 50 cigarette brands from 5 manufacturers. Ammonia levels ranged from approximately 1μg to 23μg per cigarette for ISO smoking conditions and 38μg to 67μg per cigarette for Canadian intense smoking conditions and statistically significance differences were observed between brands and manufacturers. Our findings suggest that ammonia levels vary by brand and are higher under Canadian intense smoking conditions.

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“…Ammonia was trapped on a glass fiber filter and a wash bottle connected in series. The glass fiber filter was extracted with the content of the wash bottle, derivatized with dansyl chloride, and analyzed by HPLC with a tandem mass spectrometer (HPLC/MS-MS) (32). Volatile N-nitrosamines were collected on a glass fiber filter and in two wash bottles containing a citrate/phosphate buffer solution with ascorbic acid to inhibit artificial generation of N-nitrosamines.…”

Section: Mainstream Smoke Chemistrymentioning

confidence: 99%

Mainstream Smoke Chemistry and in Vitro and In Vivo Toxicity of the Reference Cigarettes 3R4F and 2R4F

Roemer

Schramke

Weiler

et al. 2012

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

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A new reference cigarette, the 3R4F, has been developed to replace the depleting supply of the 2R4F cigarette. The present study was designed to compare mainstream smoke chemistry and toxicity of the two reference cigarettes under the International Organization for Standardization (ISO) machine smoking conditions, and to further compare mainstream smoke chemistry and toxicological activity of the 3R4F cigarette by two different smoking regimens, i.e., the machine smoking conditions specified by ISO and the Health Canada intensive (HCI) smoking conditions.The in vitro cytotoxicity and mutagenicity was determined in the neutral red uptake assay, the Salmonella reverse mutation assay, and the mouse lymphoma thymidine kinase assay. Additionally, a 90-day nose-only inhalation study in rats was conducted to assess the in vivo toxicity. The comparison of smoke chemistry between the two reference cigarettes found practically the same yields of total particulate matter (TPM), ‘tar’, nicotine, carbon monoxide, and most other smoke constituents. For both cigarettes, the in vitro cytotoxicity, mutagenicity, and in vivo toxicity showed the expected smoke-related effects compared to controls without smoke exposure. There were no meaningful differences between the 2R4F and 3R4F regarding these toxicological endpoints. The assessments for the 3R4F cigarette by smoking regimen found as a trivial effect, due to the higher amount of smoke generated per cigarette under HCI conditions, an increased yield of toxicant and higher toxicological activity per cigarette. However, per mg TPM, ‘tar’, or nicotine, the amounts of toxicants and the in vitro toxicity were generally lower under HCI conditions, but the in vivo activity was not different between the two machine smoking conditions. Overall, as the main result, the present study suggests equivalent smoke chemistry and in vitro and in vivo toxicity for the 2R4F and 3R4F reference cigarettes.

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Evaluation of Two Derivatization Reagents for the Determination by LC-MS/MS of Ammonia in Cigarette Mainstream Smoke

Cited by 12 publications

References 40 publications

Critical role for arginase 2 in obesity-associated pancreatic cancer

Critical role for arginase 2 in obesity-associated pancreatic cancer

Method for the Determination of Ammonia in Mainstream Cigarette Smoke Using Ion Chromatography

Mainstream Smoke Chemistry and in Vitro and In Vivo Toxicity of the Reference Cigarettes 3R4F and 2R4F

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