A cross-sectional investigation of biomarkers of risk after a decade of smoking

Calapai, Gioacchino; Caputi, Achille P.; Mannucci, Carmen; Gregg, Evan O.; Pieratti, Antonella; Russo, G; Chaudhary, Nveed; Puntoni, Riccardo; Lowe, Frazer; McEwan, Michael; Bassi, Antonella; Morandi, Stefania; Nunziata, Alfredo

doi:10.3109/08958370902798455

Cited by 29 publications

(34 citation statements)

References 21 publications

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“…The decreased plasma DHA in SMK and MSC suggest impaired antioxidant and anti-inflammatory ability [46]. Arachidonic acid metabolism is a key pathway in regulation of inflammatory responses, and several studies, including our data [53] have shown elevated levels of isoprostanes, lipoxygenase metabolites such as 12-HETE, and leukotrienes in smokers [10,[47][48][49]. Metabolomic profiles presented herein show changes in the levels of arachidonic acid in plasma and saliva and salivary 12-HETE (Figure 2) among the study groups.…”

Section: Discussionmentioning

confidence: 55%

“…Many of the BioExp (nicotine and its metabolites and the combustion biomarkers) have been validated in smokers and non-tobacco consumers [10,11], and in moist snuff consumers as well [53]. Qualification of other differentiating metabolites reported herein is in progress.…”

Section: Discussionmentioning

confidence: 92%

“…Existing epidemiological studies show that the relative risk of several diseases is significantly reduced with moist snuff consumption compared to smoking, although the disease risks are somewhat higher than non-smokers. A number of biomarkers that indicate exposure (termed biomarkers of exposure, BioExp) to nicotine, as well as the toxicants present in smoke and tobacco, have been described [10,11]. In contrast, there is limited information on the biomarkers of effect (BioEff ) that indicates the effect (s) of exposure to different categories of tobacco products.…”

Section: Introductionmentioning

confidence: 99%

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Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

Prasad¹,

Jones²,

Schmidt³

et al. 2015

J Metabolomics

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Background: The existing US epidemiological data show that long-term cigarette smokers are at higher risk of developing serious diseases relative to moist snuff consumers. To understand the effects of tobacco consumption, global metabolomic profiles were generated. Here, we describe metabolomic changes in oxidative stress and inflammation pathways. Methods: Matching plasma, urine, and saliva samples from chronic/long-term smokers (SMK), moist snuff consumers (MSC), and non-tobacco consumers (NTC), 40 subjects in each cohort, were collected in a crosssectional biomarker discovery study. Untargeted metabolomics and data analyses were performed using Metabolon's proprietary technology. Results: Several biochemicals that significantly differed between study cohorts were identified in all three matrices, with most metabolites found in urine. Random forest analyses of the metabolomes grouped study subjects with a high accuracy and indicated that nicotine and its metabolites primarily drive separation between the NTC and MSC; otherwise, metabolomic profiles of NTC and MSC are more similar to each other, and SMK appear to manifest a distinct metabolomic profile. SMK exhibit lower levels of antioxidants, changes in glutathione metabolism and purine degradation pathways, docosahexaenoate, arachidonate, and 12-hydroxyeicosatetraenoic acid, suggesting increased oxidative stress and inflammation relative to MSC and NTC. Conclusions: Metabolomic profiles show that while SMK and MSC cohorts exhibit higher levels of nicotine and its metabolites, SMK manifest evidence of increased oxidative stress and inflammation relative to MSC and NTC. These observed biochemical changes in the SMK could be likely due to the combustion-related toxicants present in cigarette smoke. Impact: Several differentiating metabolites identified herein could be utilized as potential biomarkers of effect. Further, the metabolomic profiles improve our understanding of biological changes in tobacco consumers.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

Prasad¹,

Jones²,

Schmidt³

et al. 2015

J Metabolomics

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“…The synthesis of TxA 2 by TxAS is dependent on COX activities as COX-1 and COX-2 provide TxAS with the substrate, prostaglandin H 2 (Nie et al, 2004). In addition, it has been recently demonstrated that nicotine plus its five major metabolites were significantly elevated in smokers when compared with non-smokers, with a significant high level of TxB 2 (Calapai et al, 2009). Thus, it is reasonable to postulate that NNK stimulates TxA 2 synthesis in lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor

Huang

Hsin

et al. 2010

Oncogene

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The role of thromboxane A 2 (TxA 2 ) in smokingassociated lung cancer is poorly understood. This study was conducted to study the role of TxA 2 in smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-promoted cell survival and growth in human lung cancer cells. We found that NNK increased TxA 2 synthase (TxAS) expression and thromboxane B 2 (TxB 2 ) generation in cultured lung cancer cells, the result of which was supported by the increased level of TxAS in lung cancer tissues of smokers. Both TxAS-specific inhibitor furegrelate and TxA 2 receptor antagonist SQ29548 completely blocked NNK-mediated cell survival and growth via inducting apoptosis. TxA 2 receptor agonist U46619 reconstituted a near-full survival and growth response to NNK when TxAS was inhibited, affirming the role of TxA 2 receptor in NNK-mediated cell survival and growth. Suppression of cyclic adenosine monophosphate response element binding protein (CREB) activity by its small interference RNA blocked the effect of NNK. Phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) also had a positive role. Altogether, our results have revealed that NNK stimulates TxA 2 synthesis and activates its receptor in lung cancer cells. The increased TxA 2 may then activate CREB through PI3K/Akt and extracellular ERK pathways, thereby contributing to the NNK-promoted survival and growth of lung cancer cells.

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“…This could rise to 1 billion deaths during the 21st century [2]. Smoking is associated with circulatory and vascular alterations, including atherosclerosis [3], endothelial dysfunction [4], altered blood lipid profile [5], increased platelet aggregation [6] and oxidative stress-associated biomarkers of inflammation [7]. However, the mechanisms by which smoking influences atherosclerosis, and in particular coronary artery disease (CAD), are still not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease

et al. 2011

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A cross-sectional investigation of biomarkers of risk after a decade of smoking

Cited by 29 publications

References 21 publications

Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers

4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor

Smoking and FOS expression from blood leukocyte transcripts in patients with coronary artery disease

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