46 results on '"Chen, Menglan"'
Search Results
2. Faster liquid chromatography-tandem mass spectrometry method for analysis of isomeric urinary mercapturic acid metabolites of crotonaldehyde, methacrolein, and methyl vinyl ketone
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Chen, Menglan, Carmella, Steven G., Zhao, Yingchun, and Hecht, Stephen S.
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- 2024
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3. Distribution of mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes variants associated with hearing loss in Southwestern China
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Zhou, Shiyu, Chen, Menglan, Pei, Jiahong, Zhang, Chen, Ren, Xiaofei, Li, Jingyu, Sa, Yaliang, Zhu, Baosheng, and Li, Yunlong
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- 2024
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4. Effective Adsorption of Pb2+ on Porous Carbon Derived from Functional Octadecahedron ZIF-8
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Chen, Menglan, Wang, Hongxia, Song, Fangxiang, Zeng, Xian, Wu, Nian, Luo, Honghuan, Cai, Xiaoqin, and Li, Yan
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- 2022
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5. The role of ferroptosis in chronic intermittent hypoxia-induced lung injury
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Chen, Jia, Zhu, Huixin, Chen, Qin, Yang, Yisong, Chen, Mengxue, Huang, Jiefeng, Chen, Menglan, and Lian, Ningfang
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- 2022
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6. The role of platelet-related parameters for the prediction of NAFLD in OSAHS patients
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Chen, Menglan, Wang, Biying, Huang, Jiefeng, Zhao, Jianming, Chen, Jia, and Chen, Gongping
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- 2022
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7. Assessment of formaldehyde levels in relation to respiratory and allergic symptoms in children from Alba County schools, Romania
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Neamtiu, Iulia A., Lin, Shao, Chen, Menglan, Roba, Carmen, Csobod, Eva, and Gurzau, Eugen S.
- Published
- 2019
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8. Levels of Urinary Mercapturic Acids of Acrolein, Methacrolein, Crotonaldehyde, and Methyl Vinyl Ketone in Relationship to Chronic Obstructive Pulmonary Disease in Cigarette Smokers of the Subpopulations and Intermediate Outcome Measures in COPD Study...
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Wendt, Chris H., Bowler, Russell P., Demorest, Connor, Hastie, Annette, Labaki, Wassim W., Chen, Menglan, Carmella, Steven G., and Hecht, Stephen S.
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- 2023
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9. Evaluation of Toxicant and Carcinogen Metabolites in the Urine of E-Cigarette Users Versus Cigarette Smokers
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Hecht, Stephen S., Carmella, Steven G., Kotandeniya, Delshanee, Pillsbury, Makenzie E., Chen, Menglan, Ransom, Benjamin W. S., Vogel, Rachel Isaksson, Thompson, Elizabeth, Murphy, Sharon E., and Hatsukami, Dorothy K.
- Published
- 2015
10. Children’s Exposure to Secondhand and Thirdhand Smoke Carcinogens and Toxicants in Homes of Hookah Smokers
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Kassem, Nada O. F., Daffa, Reem M., Liles, Sandy, Jackson, Sheila R., Kassem, Noura O., Younis, Maram A., Mehta, Setoo, Chen, Menglan, Jacob, Peyton, Carmella, Steve G., Chatfield, Dale A., Benowitz, Neal L., Matt, Georg E., Hecht, Stephen S., and Hovell, Melbourne F.
- Published
- 2014
11. High throughput liquid chromatography–tandem mass spectrometry assay for mercapturic acids of acrolein and crotonaldehyde in cigarette smokers’ urine
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Carmella, Steven G., Chen, Menglan, Zarth, Adam, and Hecht, Stephen S.
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- 2013
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12. Increased Levels of the Acrolein Metabolite 3‑Hydroxypropyl Mercapturic Acid in the Urine of e‑Cigarette Users.
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Chen, Menglan, Carmella, Steven G., Lindgren, Bruce R., Luo, Xianghua, Ikuemonisan, Joshua, Niesen, Brittany, Thomson, Nicole M., Murphy, Sharon E., Hatsukami, Dorothy K., and Hecht, Stephen S.
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- 2023
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13. Corn‐like mSiO2@ZIF‐8 Composite Load with Curcumin for Target Cancer Drug‐Delivery System.
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Chen, Menglan, Song, Fangxiang, Wu, Nian, Luo, Honghuan, Cai, Xiaoqin, and Li, Yan
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CURCUMIN , *MESOPOROUS silica , *DRUG delivery systems , *ANTINEOPLASTIC agents , *FOLIC acid , *SOL-gel processes - Abstract
To improve the drug loading rate of mesoporous silica (mSiO2), mSiO2 nanorods were synthesized by a modified sol‐gel method, then mSiO2@ZIF‐8 nanoparticles were prepared by using mSiO2 nanorods as the matrix. The structure of mSiO2 and mSiO2@ZIF‐8 were characterized. The results show that mSiO2@ZIF‐8 nanoparticles are corn‐like, with a specific surface area of 116.81 m2 g−1, pore volume of 0.31 cm3 g−1, and pore size of 8.43 nm. Curcumin (CUR) was used as an anti‐tumor model drug in drug delivery experiments. The drug loading rate of mSiO2@ZIF‐8 for CUR is 21.39 %. Before modification by Chitosan (CS) and folic acid (FA), the cumulative release rate of CUR is 30.27 % at pH 5.6 and 26.26 % at pH 7.4. After been target functionalized by CS and FA. At pH 5.6 and pH 7.4, the cumulative release rates are 34.21 % and 20.48 %, respectively, within 228 h after drug release in vitro. The results show that the drug delivery system has good pH responsiveness. Zero‐order, first‐order, Higuchi, Hixson Crowell, and Korsmeyer Peppas models were used to describe the release kinetics of mSiO2@ZIF‐8@CUR. The Higuchi model provides the highest fit for the CUR release of mSiO2@ZIF‐8@CUR. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. Effective Adsorption of Pb2+ on Porous Carbon Derived from Functional Octadecahedron ZIF-8.
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Chen, Menglan, Wang, Hongxia, Song, Fangxiang, Zeng, Xian, Wu, Nian, Luo, Honghuan, Cai, Xiaoqin, and Li, Yan
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- 2022
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15. Photography in China: Science, Commerce and Communication.
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Chen, Menglan
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PHOTOGRAPHY ,NONFICTION - Published
- 2024
16. Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer.
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Park, Sungshim L., Le Marchand, Loic, Cheng, Guang, Balbo, Silvia, Chen, Menglan, Carmella, Steven G., Thomson, Nicole M., Lee, Younghan, Patel, Yesha M., Stram, Daniel O., Jensen, Joni, Hatsukami, Dorothy K., Murphy, Sharon E., and Hecht, Stephen S.
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- 2022
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17. Urinary levels of volatile organic carcinogen and toxicant biomarkers in relation to lung cancer development in smokers
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Yuan, Jian-Min, Gao, Yu-Tang, Wang, Renwei, Chen, Menglan, Carmella, Steven G., and Hecht, Stephen S.
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- 2012
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18. Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China
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Kensler, Thomas W., Ng, Derek, Carmella, Steven G., Chen, Menglan, Jacobson, Lisa P., Muñoz, Alvaro, Egner, Patricia A., Chen, Jian Guo, Qian, Geng Sun, Chen, Tao Yang, Fahey, Jed W., Talalay, Paul, Groopman, John D., Yuan, Jian-Min, and Hecht, Stephen S.
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- 2012
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19. Large Differences in Urinary Benzene Metabolite S-Phenylmercapturic Acid Quantitation: A Comparison of Five LC–MS-MS Methods.
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Tevis, Denise S, Willmore, Andrew, Bhandari, Deepak, Bowman, Brett, Biren, Chloe, Kenwood, Brandon M, Jacob, Peyton, Liu, Jia, Bello, Kristina, Hecht, Stephen S, Carmella, Steven G, Chen, Menglan, Gaudreau, Eric, Bienvenu, Jean-François, Blount, Benjamin C, and Jesús, Víctor R De
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BENZENE ,QUALITY control ,BIOMARKERS ,ACIDS ,URINE - Abstract
Benzene is a known genotoxic carcinogen linked to many hematological abnormalities. S-phenylmercapturic acid (PHMA, N -acetyl- S -(phenyl)- L -cysteine, CAS# 4775-80-8) is a urinary metabolite of benzene and is used as a biomarker to assess benzene exposure. Pre-S-phenylmercapturic acid (pre-PHMA) is a PHMA precursor that dehydrates to PHMA at acidic pH. Published analytical methods that measure urinary PHMA adjust urine samples to a wide range of pH values using several types of acid, potentially leading to highly variable results depending on the concentration of pre-PHMA in a sample. Information is lacking on the variation in sample preparation among laboratories regularly measuring PHMA and the effect of those differences on PHMA quantitation in human urine samples. To investigate the differences in PHMA quantitation, we conducted an inter-laboratory comparison that included the analysis of 50 anonymous human urine samples (25 self-identified smokers and 25 self-identified non-smokers), quality control samples and commercially available reference samples in five laboratories using different analytical methods. Observed urinary PHMA concentrations were proportionally higher at lower pH, and results for anonymous urine samples varied widely among the methods. The method with the neutral preparation pH yielded results about 60% lower than the method using the most acidic conditions. Samples spiked with PHMA showed little variation, suggesting that the variability in results in human urine samples across methods is driven by the acid-mediated conversion of pre-PHMA to PHMA. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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20. Ethylation and methylation of hemoglobin in smokers and non-smokers
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Carmella, Steven G., Chen, Menglan, Villalta, Peter W., Gurney, James G., Hatsukami, Dorothy K., and Hecht, Stephen S.
- Published
- 2002
21. Metabolites of a Tobacco-Specific Carcinogen in Urine From Newborns
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Lackmann, Gerd M., Salzberger, Ulrich, Töllner, Uwe, Chen, Menglan, Carmella, Steven G., and Hecht, Stephen S.
- Published
- 1999
22. Urinary Cyanoethyl Mercapturic Acid, a Biomarker of the Smoke Toxicant Acrylonitrile, Clearly Distinguishes Smokers From Nonsmokers.
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Luo, Xianghua, Carmella, Steven G, Chen, Menglan, Jensen, Joni A, Wilkens, Lynne R, Marchand, Loic Le, Hatsukami, Dorothy K, Murphy, Sharon E, Hecht, Stephen S, and Le Marchand, Loic
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BIOMARKERS ,LIQUID chromatography-mass spectrometry ,ACRYLONITRILE ,TOBACCO products ,RECEIVER operating characteristic curves ,MENTHOL ,URINE proteins - Abstract
Introduction: Cyanoethyl mercapturic acid (CEMA) is a urinary metabolite of acrylonitrile, a toxicant found in substantial quantities in cigarette smoke, but not in non-combusted products such as e-cigarettes or smokeless tobacco and rarely in the diet or in the general human environment. Thus, we hypothesized that CEMA is an excellent biomarker of combusted tobacco product use.Aims and Methods: We tested this hypothesis by analyzing CEMA in the urine of 1259 cigarette smokers (urinary cotinine ≥25 ng/mL) and 1191 nonsmokers. The analyses of CEMA and cotinine were performed by validated liquid chromatography-tandem mass spectrometry methods. Logistic regression was fit for log-transformed CEMA to construct the receiver operating characteristic curve.Results: We found that a CEMA cutpoint of 27 pmol/mL urine differentiated cigarette smokers from nonsmokers with sensitivity and specificity greater than 99%. The use of different cotinine cutpoints to define smokers (10-30 ng/mL) had little effect on the results.Conclusions: CEMA is a highly reliable urinary biomarker to identify users of combusted tobacco products such as cigarettes as opposed to users of non-combusted products, medicinal nicotine, or nonusers of tobacco products.Implications: CEMA can be used to distinguish users of combusted tobacco products from non-combusted products such as e-cigarettes, smokeless tobacco, and medicinal nicotine. Levels of CEMA in the urine of people who use these non-combusted products are extremely low, in contrast to cotinine. [ABSTRACT FROM AUTHOR]- Published
- 2020
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23. A Randomized Clinical Trial of Snus Examining the Effect of Complete Versus Partial Cigarette Substitution on Smoking-Related Behaviors, and Biomarkers of Exposure.
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Meier, Ellen, Lindgren, Bruce R, Anderson, Amanda, Reisinger, Sarah A, Norton, Kaila J, Jensen, Joni, Strayer, Lori, Dick, Laura, Tang, Mei-Kuen, Chen, Menglan, Carmella, Steven G, Hecht, Stephen S, Murphy, Sharon E, Yang, Jing, Stepanov, Irina, O'Connor, Richard J, Shields, Peter G, and Hatsukami, Dorothy K
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CLINICAL trials ,CIGARETTES ,VOLATILE organic compounds ,CIGARETTE smokers ,CARBON monoxide - Abstract
Introduction: This 8-week multisite, randomized controlled trial of snus examined the differential effects of instructions on (1) snus use, (2) smoking and smoking-related measures, and (3) exposure to tobacco-related constituents.Method: US adult daily cigarette smokers (n = 150; 43.3% female; Medianage = 43.5) were recruited from Minneapolis, Minnesota; Columbus and Coshocton, Ohio; and Buffalo, New York. Following a 1-week sampling phase of snus, participants who used at least 7 pouches were randomized to either (1) partial substitution (PS; "use snus as you like with your cigarettes"), (2) complete substitution (CS; "avoid cigarettes"), or (3) usual brand cigarettes (UB). Analyses included between-group analyses (eg, PS vs. CS) using Wilcoxon rank sum test of cigarettes per day and snus pouches per day, and a linear mixed model (biomarkers).Results: Compared to the PS and UB groups, smokers assigned to CS reported greater reductions in cigarettes per day (ps < .001), using more snus pouches per day (p = .02), and more smoke-free days (CS median = 14.5, PS and UB medians = 0, p < .001). In addition, results demonstrated reductions in carbon monoxide (p < .001), total nicotine equivalents (p = .02), and four out of five measured volatile organic compounds (ps < .01) over time among the CS group. Exposure to N'-nitrosonornicotine increased by trial end only among the PS group (p < .04). Phenanthrene tetraol increased among all groups by trial end (p = .02) with no difference between groups.Conclusions: Instructions to completely switch from cigarettes to snus resulted in the greatest reduction in cigarettes and exposure to harmful constituents.Implications: Directly instructing smokers to switch completely to snus, rather than using ad libitum (with no instructions to avoid cigarettes), is necessary for reductions in smoking and subsequent exposure to harmful constituents. [ABSTRACT FROM AUTHOR]- Published
- 2020
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24. Adapting Marketing Communication for Sub Saharan Africa / The Case of Procera Networks
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Nabil, Anam and Chen, Menglan
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Social Sciences ,Samhällsvetenskap - Published
- 2015
25. Longitudinal stability in cigarette smokers of urinary biomarkers of exposure to the toxicants acrylonitrile and acrolein.
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Chen, Menglan, Carmella, Steven G., Sipe, Chistopher, Jensen, Joni, Luo, Xianghua, Le, Chap T., Murphy, Sharon E., Benowitz, Neal L., McClernon, F. Joseph, Vandrey, Ryan, Allen, Sharon S., Denlinger-Apte, Rachel, Cinciripini, Paul M., Strasser, Andrew A., al’Absi, Mustafa, Robinson, Jason D., Donny, Eric C., Hatsukami, Dorothy, and Hecht, Stephen S.
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CIGARETTE smokers , *ACRYLONITRILE , *ACROLEIN , *METABOLITES , *MERCAPTURIC acid - Abstract
The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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26. Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial.
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Hatsukami, Dorothy K., Luo, Xianghua, Jensen, Joni A., al’Absi, Mustafa, Allen, Sharon S., Carmella, Steven G., Chen, Menglan, Cinciripini, Paul M., Denlinger-Apte, Rachel, Drobes, David J., Koopmeiners, Joseph S., Lane, Tonya, Le, Chap T., Leischow, Scott, Luo, Kai, McClernon, F. Joseph, Murphy, Sharon E., Paiano, Viviana, Robinson, Jason D., and Severson, Herbert
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CIGARETTES ,TOBACCO composition ,NICOTINE addiction ,PROPAFENONE ,NICOTINE addiction treatment ,SMOKING cessation ,BIOLOGICAL tags ,POLYCYCLIC aromatic hydrocarbons ,CARBON monoxide analysis ,BREATH tests ,COMPARATIVE studies ,CREATININE ,DRUG withdrawal symptoms ,HYDROCARBONS ,RESEARCH methodology ,MEDICAL cooperation ,NICOTINE ,PHARMACOKINETICS ,RESEARCH ,RESEARCH funding ,SMOKE ,SUBSTANCE abuse ,TOBACCO ,EVALUATION research ,TOBACCO products ,RANDOMIZED controlled trials ,BLIND experiment ,ACETYLCYSTEINE - Abstract
Importance: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined.Objectives: To determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure.Design, Setting, and Participants: A double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017.Interventions: (1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes.Main Outcomes and Measures: Between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention.Results: Among 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93]; P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, -3.38 [95% CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92]; P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, -0.31 to 1.67]; P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06]; P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04]; P = .52).Conclusions and Relevance: Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control.Trial Registration: clinicaltrials.gov Identifier: NCT02139930. [ABSTRACT FROM AUTHOR]- Published
- 2018
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27. Benzene Uptake and Glutathione S-transferase T1 Status as Determinants of S-Phenylmercapturic Acid in Cigarette Smokers in the Multiethnic Cohort.
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Haiman, Christopher A., Patel, Yesha M., Stram, Daniel O., Carmella, Steven G., Chen, Menglan, Wilkens, Lynne R., Le Marchand, Loic, and Hecht, Stephen S.
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LUNG cancer risk factors ,BENZENE ,GLUTATHIONE transferase ,CIGARETTE smokers ,COHORT analysis ,URINALYSIS ,MERCAPTURIC acid - Abstract
Research from the Multiethnic Cohort (MEC) demonstrated that, for the same quantity of cigarette smoking, African Americans and Native Hawaiians have a higher lung cancer risk than Whites, while Latinos and Japanese Americans are less susceptible. We collected urine samples from 2,239 cigarette smokers from five different ethnic groups in the MEC and analyzed each sample for S-phenylmercapturic acid (SPMA), a specific biomarker of benzene uptake. African Americans had significantly higher (geometric mean [SE] 3.69 [0.2], p<0.005) SPMA/ml urine than Whites (2.67 [0.13]) while Japanese Americans had significantly lower levels than Whites (1.65 [0.07], p<0.005). SPMA levels in Native Hawaiians and Latinos were not significantly different from those of Whites. We also conducted a genome-wide association study in search of genetic risk factors related to benzene exposure. The glutathione S-transferase T1 (GSTT1) deletion explained between 14.2–31.6% (p = 5.4x10
-157 ) and the GSTM1 deletion explained between 0.2%-2.4% of the variance (p = 1.1x10-9 ) of SPMA levels in these populations. Ethnic differences in levels of SPMA remained strong even after controlling for the effects of these two deletions. These results demonstrate the powerful effect of GSTT1 status on SPMA levels in urine and show that uptake of benzene in African American, White, and Japanese American cigarette smokers is consistent with their lung cancer risk in the MEC. While benzene is not generally considered a cause of lung cancer, its metabolite SPMA could be a biomarker for other volatile lung carcinogens in cigarette smoke. [ABSTRACT FROM AUTHOR]- Published
- 2016
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28. Determination of carbendazim and metiram pesticides residues in reapeseed and peanut oils by fluorescence spectrophotometry.
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Chen, Menglan, Zhao, Zhimin, Lan, Xiufeng, Chen, Yuming, Zhang, Lin, Ji, Rendong, and Wang, Lexin
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CARBENDAZIM , *SEEDS , *FLUORESCENCE spectroscopy , *PESTICIDES , *MIXTURES , *COEFFICIENTS (Statistics) - Abstract
Fluorescence spectrophotometry was applied to the determination of pesticide residue (carbendazim and metiram) in edible oil (rapeseed oil and peanut oil). Based on the fluorescence spectra of the oil–pesticide mixture, the prediction models between fluorescence intensity and pesticide content can be obtained. Functional relationship were found between fluorescence intensity and concentration of pesticide in the mixture and the correlation coefficient were greater than 0.99. We can calculate the detection limit is 7.07 × 10 −4 mg/mL for rapeseed oil and 9.28 × 10 −4 mg/mL for peanut oil, respectively. The prediction experiments show that the percent recovery range from 92.5% to 108.2%. It was verified that the fluorescence spectrophotometry method in this paper was feasible to detect the pesticide residues in edible oil. This study provides a new way for the detection of pesticide residues. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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29. Mercapturic Acids Derived from the Toxicants Acrolein and Crotonaldehyde in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer.
- Author
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Park, Sungshim L., Carmella, Steven G., Chen, Menglan, Patel, Yesha, Stram, Daniel O., Haiman, Christopher A., Le Marchand, Loic, and Hecht, Stephen S.
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LUNG cancer risk factors ,MERCAPTURIC acid ,ACROLEIN ,CROTONALDEHYDE ,URINALYSIS ,CIGARETTE smokers - Abstract
The Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans and Native Hawaiians have a higher risk for lung cancer whereas Latinos and Japanese Americans have a lower risk. Acrolein and crotonaldehyde are two important constituents of cigarette smoke which have well documented toxic effects and could play a role in lung cancer etiology. Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA) and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA), respectively, are validated biomarkers of acrolein and crotonaldehyde exposure. We quantified levels of 3-HPMA and HMPMA in the urine of more than 2200 smokers from these five ethnic groups, and also carried out a genome wide association study using blood samples from these subjects. After adjusting for age, sex, creatinine, and total nicotine equivalents, geometric mean levels of 3-HPMA and HMPMA were significantly different in the five groups (P<0.0001). Native Hawaiians had the highest and Latinos the lowest geometric mean levels of both 3-HPMA and HMPMA. Levels of 3-HPMA and HMPMA were 3787 and 2759 pmol/ml urine, respectively, in Native Hawaiians and 1720 and 2210 pmol/ml urine in Latinos. These results suggest that acrolein and crotonaldehyde may be involved in lung cancer etiology, and that their divergent levels may partially explain the differing risks of Native Hawaiian and Latino smokers. No strong signals were associated with 3-HPMA in the genome wide association study, suggesting that formation of the glutathione conjugate of acrolein is mainly non-enzymatic, while the top significant association with HMPMA was located on chromosome 12 near the TBX3 gene, but its relationship to HMPMA excretion is not clear. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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30. Elevated Levels of Mercapturic Acids of Acrolein and Crotonaldehyde in the Urine of Chinese Women in Singapore Who Regularly Cook at Home.
- Author
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Hecht, Stephen S., Koh, Woon-Puay, Wang, Renwei, Chen, Menglan, Carmella, Steven G., Murphy, Sharon E., and Yuan, Jian-Min
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MERCAPTURIC acid ,ACROLEIN ,CROTONALDEHYDE ,URINALYSIS ,CHINESE women ,LUNG cancer ,CANCER in women - Abstract
Lung cancer is unusually common among non-smoking women in Southeastern Asia but the causes of this frequently fatal disease are not well understood. Several epidemiology studies indicate that inhalation of fumes from high temperature Chinese style cooking with a wok may be a cause. Only one previous study investigated uptake of potential toxicants and carcinogens by women who cook with a wok. We enrolled three-hundred twenty-eight non-smoking women from Singapore for this study. Each provided a spot urine sample and answered a questionnaire concerning their cooking habits and other factors. The urine samples were analyzed by liquid chromatography-tandem mass spectrometry for mercapturic acid metabolites of acrolein (3-hydroxypropylmercapturic acid), crotonaldehyde (3-hydroxy-1-methylpropylmercapturic acid), and benzene (S-phenylmercapturic acid), accepted biomarkers of uptake of these toxic and carcinogenic compounds. We observed statistically significant effects of wok cooking frequency on levels of 3-hydroxypropylmercapturic acid and 3-hydroxy-1-methylpropylmercapturic acid, but not S-phenylmercapturic acid. Women who cooked greater than 7 times per week had a geometric mean of 2600 (95% CI, 2189-3090) pmol/mg creatinine 3-hydroxypropylmercapturic acid compared to 1901 (95% CI, 1510-2395) pmol/mg creatinine when cooking less than once per week (P for trend 0.018). The corresponding values for 3-hydroxy-1-methylpropylmercapturic acid were 1167 (95% CI, 1022-1332) and 894 (95% CI, 749-1067) pmol/mg creatinine (P for trend 0.008). We conclude that frequent wok cooking leads to elevated exposure to the toxicants acrolein and crotonaldehyde, but not benzene. Kitchens should be properly ventilated to decrease exposure to potentially toxic and carcinogenic fumes produced during Chinese style wok cooking. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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31. Enantiomeric composition of N′-nitrosonornicotine and N′-nitrosoanatabine in tobacco.
- Author
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Carmella, Steven G., McIntee, Edward J., Chen, Menglan, and Hecht, Stephen S.
- Abstract
The tobacco-specific nitrosamines N′-nitrosonornicotine (NNN) and N′-nitrosoanatabine (NAT) are found in substantial quantities in unburned tobacco. Although this has been documented in many previous studies, no data are available on the enantiomeric composition of these nitrosamines, which both have a chiral center at their 2′-positions. We used chiral stationary phase gas chromatography with nitrosamine-selective detection to determine the enantiomeric composition of NNN and NAT in moist snuff, chewing tobacco, and cigarette tobacco. (S)-NNN comprised 75.0 ± 8.83% (SD) (n = 12) of total NNN while (S)-NAT comprised 82.6 ± 1.44% (n = 12) of total NAT. Levels of the (S)-enantiomers of NNN and NAT were generally similar to those of the corresponding secondary amines, nornicotine and anatabine, suggesting a precursor to product relationship. Nitrosation of (S)-nicotine at pH 7.0 produced >99% (S)-NNN. These results suggest that nornicotine is a significant precursor of NNN in tobacco. The results of this study provide new insights into the structures and precursors of tobacco-specific nitrosamines in tobacco products. [ABSTRACT FROM PUBLISHER]
- Published
- 2000
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32. Correction to Effects of Smoking Cessation on Eight Urinary Tobacco Carcinogen and Toxicant Biomarkers.
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Carmella, Steven G., Chen, Menglan, Han, Shaomei, Briggs, Anna, Jensen, Joni, Hatsukami, Dorothy K., and Hecht, Stephen S.
- Published
- 2012
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33. A novel method of damage model recognition for intelligent composite structures based on double-fiber sensors network.
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Shen, Lingbin, Zhao, Zhimin, Chen, Menglan, Zhu, Xingyue, and Yu, Yinshan
- Subjects
- *
PATTERN recognition systems , *ARTIFICIAL intelligence , *COMPOSITE structures , *OPTICAL fiber detectors , *MATERIALS science - Abstract
Fiber optic smart composite structures technologies have become one of the key technologies in material science. The smart composite structure is used to estimate damage states. But it is difficult to detect the internal damage with little or no indication on the surface of the composite structures. In this paper, we proposed a method for identification of different damage model of composite structures using a double-fiber sensor network. The glass fiber reinforced epoxy resin E-51 honeycomb structure composite which is commonly used in aircraft was chosen to be the base material. The smart structures employed 8-way fibers sensors. Each four-fiber as a layer were orthogonally embedded into different depth of structures. The sensors were connected to a data acquisition system based on ARM. The transmission properties of double-fiber sensors were investigated and then validated by experiments in laboratory. Here three different energy impacts damage experiments were conducted on the double-fiber smart composite structures. The results show the method based on double-fiber sensors network used for the identification of the different damage models is feasible. It has a very important reference value for the future health monitoring technology of the composite structures. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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34. Determination of rhodamine B in capsicol using the first derivative absorption spectrum.
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Ji, Rendong, Zhao, Zhimin, Yu, Xiaolei, and Chen, Menglan
- Subjects
- *
ABSORPTION spectra , *EXPONENTIAL functions , *RHODAMINE B , *REGRESSION analysis , *STANDARD deviations , *ULTRAVIOLET spectrophotometry - Abstract
Abstract In this work an analytical method for the determination of rhodamine B in capsicol was developed based on absorption spectrum. The absorption spectra were obtained about the rhodamine B-capsicol mixed solution using spectrophotometer. The experimental results show that the absorption spectra of rhodamine B-capsicol mixed solution have a stable characteristic peak at 555nm, while the first derivative absorption spectrra of the mixed solution have two characteristic peaks, and the position of the characteristic peak shifts blue with the increase of concentration of rhodamine B. Exponential and linear function regression analysis were carried out about the absorbance of characteristic peak and the concentration of Rhodamine B. Then the prediction models of Rhodamine B in capsicol were obtained. The minimum correlation coefficient was 0.9401 and the maximum was 0.9992. In addition, the recovery rate and relative standard deviation (RSD) of each model function were calculated and analysed, respectively. The results show that the exponential function is superior to the corresponding linear function, and the corresponding model function of the first derivative spectrum is superior to the model function obtained from the original spectrum. The best mean recovery rate and RSD of the original absorption spectrum is 106% and 7.658%, while the optimal result of the first derivative absorption spectra is 101% and 2.3453%, respectively. In summary, the analytical model developed allows to detect the rhodamine B in capsicol with good correlation coefficient and reproducibility, and this study provides a new way for the detection of food colorant content. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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35. Association Between Metabolic-Associated Fatty Liver Disease and Obstructive Sleep Apnea: A Cross-Sectional Study.
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Huang J, Chen L, Li X, Chen M, Lin T, and Chen G
- Abstract
Aim: Emerging evidence has revealed that obstructive sleep apnea (OSA) is an independent risk factor for the development of a variety of adverse metabolic disease states. In this study, we evaluated the association between OSA severity and metabolic dysfunction-associated fatty liver disease (MAFLD) among Asian populations., Materials and Methods: This was a cross-sectional, single-center study. The study cohort consisted of patients undergoing polysomnography and abdominal ultrasonography. Logistic regression analysis was used to evaluate the independent risk factors of MAFLD in patients with OSA., Results: A total of 1065 patients (277 non-MAFLD and 788 MAFLD) were included in the study. The prevalence of MAFLD in non-OSA, mild-moderate OSA, and severe OSA patients was 58.16%, 72.41%, and 78.0%, respectively ( p < 0.001). We identified significant differences in body mass index (BMI), apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and lowest O
2 saturation (LaSO2 ) between non-MAFLD and MAFLD patients (all p < 0.001). After adjusting for confounding variables, we used multivariate regression analysis to show that BMI, ODI, and triglyceride (TG) levels independently predicted the occurrence of MAFLD (odds ratio [OR] = 1.234, p < 0.001; OR = 1.022, p = 0.013; OR = 1.384, p = 0.001, respectively). Moreover, stratified analysis according to BMI indicated that TG levels were the predominant risk factor for MAFLD in a group of patients with a BMI < 23 kg/m2 , while BMI, ODI, TG levels, and total cholesterol (TC) were the major risk factors for MAFLD in a group of patients with a BMI ≥ 23 kg/m2 (all p < 0.05)., Conclusion: OSA-associated chronic intermittent hypoxia was independently associated with the risk of MAFLD, especially in OSA patients with a BMI ≥ 23 kg/m2 , suggesting that oxidative stress might play an important role in the pathogenesis of MAFLD in patients with OSA., Competing Interests: The authors declare that they have no competing interests in this work., (© 2023 Huang et al.)- Published
- 2023
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36. A Randomized Clinical Trial Examining the Effects of Instructions for Electronic Cigarette Use on Smoking-Related Behaviors and Biomarkers of Exposure.
- Author
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Hatsukami DK, Meier E, Lindgren BR, Anderson A, Reisinger SA, Norton KJ, Strayer L, Jensen JA, Dick L, Murphy SE, Carmella SG, Tang MK, Chen M, Hecht SS, O'connor RJ, and Shields PG
- Subjects
- Adult, Aged, Carbon Monoxide analysis, Carcinogens analysis, Cigarette Smoking adverse effects, Female, Humans, Male, Middle Aged, Young Adult, Biomarkers analysis, Cigarette Smoking metabolism, Cigarette Smoking psychology, Electronic Nicotine Delivery Systems statistics & numerical data, Smokers psychology, Smoking Cessation methods, Tobacco Use Cessation Devices statistics & numerical data
- Abstract
Introduction: Electronic cigarettes (e-cigarettes) have the potential to significantly reduce exposure to harmful constituents associated with cigarette smoking when smokers completely substitute cigarettes with e-cigarettes. This study examined patterns of e-cigarette and cigarette use, and extent of toxicant exposure, if smokers were instructed and incentivized to completely switch to e-cigarettes compared to instructions to use the product ad libitum., Aims and Methods: US adult daily smokers (n = 264; 49.2% female; Mage = 47.0), uninterested in quitting smoking immediately, were recruited from Minneapolis, MN, Columbus, OH, and Buffalo, NY. Participants were randomized to 8 weeks of instructions for (1) ad libitum use of e-cigarettes (AD-E), (2) complete substitution of cigarettes with e-cigarettes (CS-E), (3) complete substitution of cigarettes with nicotine gum or lozenge (CS-NRT), or (4) continue smoking of usual brand cigarettes (UB). Participants were incentivized for protocol compliance, including complete switching in the CS-E and CS-NRT groups. Outcome variables were cigarette smoking rate and tobacco-related biomarkers of exposure., Results: Smokers in the CS-E and CS-NRT groups showed lower rates of smoking and lower exposure to carbon monoxide, tobacco carcinogens, and other toxicants than smokers in the AD-E group. In general, no significant differences were observed between CS-E versus CS-NRT or between AD-E versus UB for most biomarkers. Significantly higher 7-day point prevalence smoke-free rates were observed for CS-E versus CS-NRT., Conclusions: Smokers instructed and incentivized to completely switch to e-cigarettes resulted in lower smoking rates and greater reductions in exposures to harmful chemicals than smokers instructed to use the product ad libitum., Implications: Smokers instructed to completely substitute e-cigarettes for cigarettes displayed significantly lower levels of smoking and biomarkers of exposure to carcinogens and toxicants, compared to smokers instructed to use e-cigarettes ad libitum and similar levels as smokers instructed to completely substitute with nicotine replacement therapies. Furthermore, a higher rate of complete switching was achieved with e-cigarettes versus nicotine replacement therapies. Approaches to maximize complete substitution with e-cigarettes are an important area for future research., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
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37. Resolution and Quantitation of Mercapturic Acids Derived from Crotonaldehyde, Methacrolein, and Methyl Vinyl Ketone in the Urine of Smokers and Nonsmokers.
- Author
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Chen M, Carmella SG, Li Y, Zhao Y, and Hecht SS
- Subjects
- Acetylcysteine chemistry, Acrolein chemistry, Acrolein urine, Aldehydes chemistry, Butanones chemistry, Humans, Molecular Structure, Acetylcysteine urine, Acrolein analogs & derivatives, Aldehydes urine, Butanones urine, Non-Smokers, Smokers
- Abstract
Using improved HPLC analysis conditions, we report the separation of three isomers of mercapturic acid conjugates previously assigned in the literature only to 3-hydroxy-1-methylpropylmercapturic acid (HMPMA-1), a human urinary metabolite of crotonaldehyde. The new conditions, employing a biphenyl column cooled to 5 °C and eluted with a gradient of formic acid, acetonitrile, and methanol, allow the analysis of human urinary mercapturic acids derived not only from crotonaldehyde but also from its isomers methacrolein (3-hydroxy-2-methylpropyl mercapturic acid, HMPMA-2) and methyl vinyl ketone (3-hydroxy-3-methylpropyl mercapturic acid, HMPMA-3). The mercapturic acids were detected and quantified by LC-ESI-MS/MS using the corresponding stable isotope labeled mercapturic acids as internal standards. The analysis was validated for accuracy and precision and applied to urine samples collected from cigarette smokers and nonsmokers. Smokers had significantly higher levels of all three mercapturic acids than did nonsmokers. The results demonstrated that HMPMA-3 from methyl vinyl ketone comprised the major portion of the peaks previously ascribed in multiple studies to HMPMA-1. HMPMA-1 had concentrations intermediate between those of HMPMA-2 and HMPMA-3 in both smokers and nonsmokers. This study reports the first quantitation of HMPMA-2 and HMPMA-3 in human urine. The observation of higher levels of HMPMA-3 than in the other two mercapturic acids suggests a previously unrecognized potential significance of methyl vinyl ketone as a toxicant in smokers and nonsmokers.
- Published
- 2020
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38. Urinary levels of cigarette smoke constituent metabolites are prospectively associated with lung cancer development in smokers.
- Author
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Yuan JM, Gao YT, Murphy SE, Carmella SG, Wang R, Zhong Y, Moy KA, Davis AB, Tao L, Chen M, Han S, Nelson HH, Yu MC, and Hecht SS
- Subjects
- Aged, China epidemiology, Female, Humans, Lung Neoplasms epidemiology, Lung Neoplasms etiology, Male, Middle Aged, Nicotine pharmacokinetics, Nitrosamines pharmacokinetics, Prospective Studies, Smoke adverse effects, Nicotiana, Cotinine urine, Lung Neoplasms urine, Nitrosamines urine, Phenanthrenes urine, Pyridines urine, Smoke analysis, Smoking adverse effects
- Abstract
Polycyclic aromatic hydrocarbons (PAH) are believed to be among the principal causative agents for lung cancer in smokers, but no epidemiologic studies have evaluated the relationship of PAH uptake and metabolism to lung cancer. In this study, we quantified prediagnostic urinary levels of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a validated biomarker of PAH uptake and metabolism, as well as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), and cotinine and its glucuronides (total cotinine), validated biomarkers of uptake of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and nicotine, respectively, in relation to lung cancer risk among current smokers in a nested case-control study within a cohort of 18,244 Chinese men in Shanghai, China. Urinary levels of PheT, total NNAL, and total cotinine were significantly higher in cases than controls (N = 476 matched pairs). ORs (95% confidence intervals) for lung cancer in the second, third, fourth, and fifth quintiles of PheT were 1.70 (1.00-2.88), 1.07 (0.62-1.84), 1.48 (0.86-2.53), and 2.34 (1.33-4.11), respectively, relative to the lowest quartile (P(trend) = 0.023) after adjustment for self-reported smoking intensity and duration and urinary total NNAL and total cotinine. This study also confirmed that urinary total NNAL and total cotinine are independently related to lung cancer risk., (©2011 AACR.)
- Published
- 2011
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39. Elevated levels of volatile organic carcinogen and toxicant biomarkers in Chinese women who regularly cook at home.
- Author
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Hecht SS, Seow A, Wang M, Wang R, Meng L, Koh WP, Carmella SG, Chen M, Han S, Yu MC, and Yuan JM
- Subjects
- China epidemiology, Chromatography, High Pressure Liquid, Female, Gas Chromatography-Mass Spectrometry, Hot Temperature, Humans, Lung Neoplasms epidemiology, Middle Aged, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry, Biomarkers urine, Carcinogens metabolism, Cooking, Lung Neoplasms chemically induced, Oils, Volatile adverse effects
- Abstract
Background: Epidemiologic studies associate lung cancer in nonsmoking Chinese women with Chinese-style wok cooking. Our goal was to quantify carcinogen and toxicant biomarkers in Chinese women who reported regularly doing home cooking compared with women randomly selected from the Singapore Chinese Health Study as controls., Methods: Biomarkers were quantified by high-performance liquid chromatography-mass spectrometry, high-performance liquid chromatography with fluorescence detection, and gas chromatography-mass spectrometry., Results: Compared with controls, women who engaged in regular home cooking had significantly higher levels of mercapturic acids of acrolein {geometric mean, 1,959 pmol/mg creatinine [95% confidence interval (95% CI), 1,554-2,467] versus 1,370 (95% CI, 1,077-1,742); P=0.038}, crotonaldehyde [geometric mean, 232 pmol/mg creatinine (95% CI, 193-277) versus 142 (95% CI, 118-171); P=0.0004], and benzene [geometric mean, 0.58 pmol/mg creatinine (95% CI, 0.44-0.78) versus 0.18 (95% CI, 0.14-0.24); P<0.0001]. No significant differences were found in levels of mercapturic acids of 1,3-butadiene, metabolites of pyrene and phenanthrene, or acetaldehyde-leukocyte DNA adduct levels between the groups. Levels of the ethylene oxide mercapturic acid were significantly higher in the controls., Conclusions: The higher levels of the mercapturic acid of benzene, a multiorgan carcinogen, in the women who cooked are particularly notable. Overall, the results showing increased exposure to the volatile toxicants and carcinogens acrolein, crotonaldehyde, and benzene in Chinese women who regularly cook provide a plausible lead for further investigating the role of volatile compounds generated during high-temperature cooking with oils as causes of lung cancer., Impact: A new direction for research on lung cancer etiology is suggested., (Copyright (c) 2010 AACR)
- Published
- 2010
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40. Effects of smoking cessation on eight urinary tobacco carcinogen and toxicant biomarkers.
- Author
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Carmella SG, Chen M, Han S, Briggs A, Jensen J, Hatsukami DK, and Hecht SS
- Subjects
- Acetylcysteine analysis, Biomarkers urine, Carcinogens toxicity, Chromatography, Liquid, Humans, Tandem Mass Spectrometry, Time Factors, Carcinogens analysis, Smoking urine, Smoking Cessation
- Abstract
We determined the persistence at various times (3, 7, 14, 21, 28, 42, and 56 days) of eight tobacco smoke carcinogen and toxicant biomarkers in the urine of 17 smokers who stopped smoking. The biomarkers were 1-hydroxy-2-(N-acetylcysteinyl)-3-butene (1) and 1-(N-acetylcysteinyl)-2-hydroxy-3-butene (2) [collectively called MHBMA for monohydroxybutyl mercapturic acid] and 1,2-dihydroxy-4-(N-acetylcysteinyl)butane (3) [DHBMA for dihydroxybutyl mercapturic acid], metabolites of 1,3-butadiene; 1-(N-acetylcysteinyl)-propan-3-ol (4, HPMA for 3-hydroxypropyl mercapturic acid), a metabolite of acrolein; 2-(N-acetylcysteinyl)butan-4-ol (5, HBMA for 4-hydroxybut-2-yl mercapturic acid), a metabolite of crotonaldehyde; (N-acetylcysteinyl)benzene (6, SPMA for S-phenyl mercapturic acid), a metabolite of benzene; (N-acetylcysteinyl)ethanol (7, HEMA for 2-hydroxyethyl mercapturic acid), a metabolite of ethylene oxide; 1-hydroxypyrene (8) and its glucuronides (1-HOP), metabolites of pyrene; and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (9) and its glucuronides (total NNAL), a biomarker of exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These biomarkers represent some of the major carcinogens and toxicants in cigarette smoke: 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, polycyclic aromatic hydrocarbons (PAH), and NNK. With the exception of DHBMA, levels of which did not change after cessation of smoking, all other biomarkers decreased significantly after 3 days of cessation (P < 0.001). The decreases in MHBMA, HPMA, HBMA, SPMA, and HEMA were rapid, nearly reaching their ultimate levels (81-91% reduction) after 3 days. The decrease in total NNAL was gradual, reaching 92% after 42 days, while reduction in 1-HOP was variable among subjects to about 50% of baseline. Since DHBMA did not change upon smoking cessation, there appear to be sources of this metabolite other than 1,3-butadiene. The results of this study demonstrate that the tobacco smoke carcinogen/toxicant biomarkers MHBMA, HPMA, HBMA, SPMA, HEMA, 1-HOP, and NNAL are related to smoking and are good indicators of the impact of smoking on human exposure to 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, PAH, and NNK.
- Published
- 2009
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41. Quantitation of acrolein-derived (3-hydroxypropyl)mercapturic acid in human urine by liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry: effects of cigarette smoking.
- Author
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Carmella SG, Chen M, Zhang Y, Zhang S, Hatsukami DK, and Hecht SS
- Subjects
- Acetylcysteine chemistry, Acetylcysteine metabolism, Acetylcysteine urine, Acrolein chemistry, Acrolein pharmacokinetics, Atmospheric Pressure, Biomarkers urine, Humans, Molecular Structure, Smoking urine, Tandem Mass Spectrometry methods, Time Factors, Acetylcysteine analogs & derivatives, Acrolein metabolism, Chromatography, Liquid methods, Spectrometry, Mass, Electrospray Ionization methods
- Abstract
Recently published data suggest that acrolein (1), a toxic but weakly carcinogenic constituent of cigarette smoke, may be involved as a causative factor for the mutations frequently observed in the p53 tumor suppressor gene in lung cancer in smokers. Biomarkers are needed to further assess the possible relationship between acrolein uptake and cancer. In this study, we analyzed (3-hydroxypropyl)mercapturic acid (3-HPMA, 2) in human urine. 3-HPMA is a major metabolite of acrolein in laboratory animals. The method employs [13C3]3-HPMA as an internal standard, with analysis and quantitation by LC-APCI-MS/MS-SRM. Clean, readily quantifiable chromatograms were obtained. The method was accurate and precise and required only 0.1 mL of urine. Median levels of 3-HPMA were significantly higher (2900 pmol/mg of creatinine, N=35) in smokers than in nonsmokers (683 pmol/mg of creatinine, N=21) (P=0.0002). The effect of smoking was further assessed by determining the levels of 3-HPMA before and after a 4 week smoking cessation period. There was a significant 78% decrease in median levels of urinary 3-HPMA after cessation (P<0.0001). The relationship between the levels of urinary 3-HPMA and those of acrolein-derived 1,N2-propanodeoxyguanosine (PdG) adducts in lung was investigated in 14 smokers. There was a significant inverse relationship between urinary 3-HPMA and alpha-hydroxy-PdG (3) but not gamma-hydroxy-PdG (4) or total adduct levels. The results of this study clearly demonstrate that acrolein uptake in smokers is significantly higher than in nonsmokers and underline the need for further investigation of the possible relationship of acrolein uptake to lung cancer.
- Published
- 2007
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42. Comparison of polymorphisms in genes involved in polycyclic aromatic hydrocarbon metabolism with urinary phenanthrene metabolite ratios in smokers.
- Author
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Hecht SS, Carmella SG, Yoder A, Chen M, Li ZZ, Le C, Dayton R, Jensen J, and Hatsukami DK
- Subjects
- Adolescent, Adult, Aged, Analysis of Variance, Aryl Hydrocarbon Hydroxylases genetics, Biomarkers, Tumor genetics, Biomarkers, Tumor urine, Cytochrome P-450 CYP1A1 genetics, Cytochrome P-450 CYP1B1, Epoxide Hydrolases genetics, Female, Genotype, Glutathione S-Transferase pi genetics, Glutathione Transferase genetics, Humans, Lung Neoplasms epidemiology, Lung Neoplasms etiology, Lung Neoplasms genetics, Lung Neoplasms metabolism, Male, Middle Aged, Minnesota, Phenanthrenes urine, Polycyclic Aromatic Hydrocarbons urine, Predictive Value of Tests, Risk Factors, Smoking adverse effects, Polycyclic Aromatic Hydrocarbons metabolism, Polymorphism, Genetic, Smoking genetics, Smoking metabolism
- Abstract
The hypothesis that interindividual differences among smokers in the metabolism of polycyclic aromatic hydrocarbons (PAH) are related to lung cancer risk has been extensively investigated in the literature. These studies have compared lung cancer risk in groups of smokers with or without polymorphisms in genes involved in PAH metabolism. We believe that carcinogen metabolite phenotyping, involving the actual measurement of PAH metabolites, would be a better way to investigate differences in lung cancer risk. With this goal in mind, we have developed methods for quantifying phenanthrene metabolites in urine. Phenanthrene is the simplest PAH with a bay region, a feature closely associated with carcinogenicity. The urinary metabolite r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) is a measure of metabolic activation, whereas phenanthrols (HOPhe) are a measure of detoxification. In this study, we quantified urinary PheT/HOPhe ratios in 346 smokers who were also genotyped for 11 polymorphisms in genes involved in PAH metabolism: CYP1A1MspI, CYP1A1I462V, CYP1B1R48G, CYP1B1A119S, CYP1B1L432V, CYP1B1N453S, EPHX1Y113H, EPHX1H139R, GSTP1I105V, GSTP1A114V, and GSTM1 null. The geometric mean molar PheT/3-HOPhe ratio was 4.08 (95% confidence interval, 3.79-4.39). Ten percent of the smokers had PheT/3-HOPhe ratios of > or =9.90. We found a significant association between the presence of the CYP1A1I462V polymorphism and high PheT/3-HOPhe ratios (P = 0.02). This effect was particularly strong in females and in combination with the GSTM1 null polymorphism. In contrast, the CYP1B1R48G and CYP1B1A119S polymorphisms were associated with significantly lower PheT/3-HOPhe ratios, particularly in Blacks. There were no consistent significant effects of any of the other polymorphisms on PheT/3-HOPhe ratios. The highest 10% of PheT/3-HOPhe ratios could not be predicted by the presence of any of the 11 polymorphisms individually or by certain combinations. The effects of the CYP1A1I462 polymorphism observed here, particularly in combination with GSTM1 null, are quite consistent with reports in the literature. However, the results of this study indicate that genotyping is not an effective way to predict PAH metabolism at least as represented by PheT/HOPhe ratios.
- Published
- 2006
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43. Longitudinal study of urinary phenanthrene metabolite ratios: effect of smoking on the diol epoxide pathway.
- Author
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Hecht SS, Chen M, Yoder A, Jensen J, Hatsukami D, Le C, and Carmella SG
- Subjects
- Adult, Analysis of Variance, Female, Humans, Longitudinal Studies, Male, Middle Aged, Urinalysis methods, Carcinogens metabolism, Phenanthrenes urine, Polycyclic Aromatic Hydrocarbons urine, Smoking
- Abstract
We have proposed that urinary phenanthrene metabolites could be used in a carcinogen metabolite phenotyping approach to identify individuals who may be susceptible to cancer induction by polycyclic aromatic hydrocarbons (PAH). In support of this proposal, we have developed methods for quantitation of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and phenanthrols (HOPhe) in human urine. PheT is the end product of the diol epoxide metabolic activation pathway of PAH, whereas HOPhe are considered as detoxification products. In this study, we investigated the longitudinal consistency of these metabolites over time in smokers and nonsmokers and compared their levels. Twelve smokers and 10 nonsmokers provided urine samples daily for 7 days, then weekly for 6 weeks. Levels of PheT, HOPhe, and PheT/HOPhe ratios were relatively constant in most individuals, with mean coefficients of variation ranging from 29.3% to 45.7%. There were no significant changes over time in levels of the metabolites or in ratios. These results indicate that a single urine sample should be sufficient when comparing phenanthrene metabolites in different groups. PheT/HOPhe ratios were significantly higher in smokers than in nonsmokers, showing that smoking induces the diol epoxide metabolic activation pathway of phenanthrene. This finding is consistent with previous studies indicating that inducibility of PAH metabolism contributes to cancer risk in smokers.
- Published
- 2005
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44. Analysis of phenanthrols in human urine by gas chromatography-mass spectrometry: potential use in carcinogen metabolite phenotyping.
- Author
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Carmella SG, Chen M, Yagi H, Jerina DM, and Hecht SS
- Subjects
- Gas Chromatography-Mass Spectrometry, Humans, Phenotype, Smoking adverse effects, Urinalysis methods, Carcinogens analysis, Carcinogens metabolism, Phenanthrenes metabolism, Phenols urine, Polycyclic Aromatic Hydrocarbons urine
- Abstract
Phenanthrene is the simplest polycyclic aromatic hydrocarbon (PAH) containing a bay region, a feature closely associated with carcinogenicity. We have proposed that measurement of phenanthrene metabolites in human urine could be used to identify interindividual differences in metabolic activation and detoxification of PAH, and that these differences may be related to cancer susceptibility in smokers and other exposed individuals. Previously, we reported a method for quantitation of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT) in human urine. trans, anti-PheT is the ultimate product of the diol epoxide metabolic activation pathway of phenanthrene. In this study, we have extended our carcinogen metabolite phenotyping approach by developing a method for quantitation of phenanthrols in human urine. PAH phenols such as phenanthrols are considered as detoxification products. After treatment of the urine by beta-glucuronidase and arylsulfatase, a fraction enriched in phenanthrols was prepared by partitioning and solid phase extraction. The phenanthrols were silylated and analyzed by gas chromatography-positive ion chemical ionization-mass spectrometry with selected ion monitoring. [ring-(13)C(6)]3-phenanthrol was used as an internal standard. Accurate and reproducible quantitation of four phenanthrols, 1-phenanthrol (1-HOPhe), 2-HOPhe, 3-HOPhe, and 4-HOPhe, was readily achieved. In smokers, mean levels of 1-HOPhe (0.96 +/- 1.2 pmol/mg creatinine) and 3-HOPhe (0.82 +/- 0.62 pmol/mg creatinine) were greater than those of 2-HOPhe (0.47 +/- 0.29 pmol/mg creatinine), and 4-HOPhe (0.11 +/- 0.07 pmol/mg creatinine). There were no significant differences between the levels of any of the phenanthrols in smokers and nonsmokers. Total levels of the quantified phenanthrols were highly correlated with those of 3-HOPhe. Ratios of phenanthrene metabolites representing activation and detoxification were calculated as trans, anti-PheT divided by 3-HOPhe. There was a 7.5-fold spread of ratios in smokers, and a 12.3-fold spread in nonsmokers, suggesting that this may be a useful parameter for distinguishing individual metabolic responses to PAH exposure.
- Published
- 2004
45. r-1,t-2,3,c-4-Tetrahydroxy-1,2,3,4-tetrahydrophenanthrene in human urine: a potential biomarker for assessing polycyclic aromatic hydrocarbon metabolic activation.
- Author
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Hecht SS, Chen M, Yagi H, Jerina DM, and Carmella SG
- Subjects
- 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide analysis, Biotransformation, Carcinogens, Environmental analysis, Gas Chromatography-Mass Spectrometry, Humans, Polycyclic Aromatic Hydrocarbons analysis, Probability, Sensitivity and Specificity, Smoking blood, Urinalysis, 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide metabolism, Biomarkers analysis, Carcinogens, Environmental adverse effects, Polycyclic Aromatic Hydrocarbons metabolism, Psoriasis blood
- Abstract
Individual differences in the metabolic activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons (PAHs) may influence cancer risk. This has been investigated in many studies using genotyping approaches, but the results to date have been inconsistent. We propose that carcinogen metabolite phenotyping would be a more reliable way to determine the role of host metabolism in PAH-related cancer. Many PAHs are metabolically activated by formation of bay-region diol epoxides. Phenanthrene, generally considered to be noncarcinogenic, is the simplest PAH with a bay region and is metabolized to diol epoxides by the same enzymes and with the same stereochemistry as the prototypic carcinogenic PAH, benzo[a]pyrene. The major end product of this metabolic activation pathway is r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT). We have developed a method for the analysis of trans, anti-PheT in human urine. r-1,t-2,4,c-3-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, syn-PheT) was used as internal standard. After hydrolysis by beta-glucuronidase and sulfatase, solid phase extraction, and high-performance liquid chromatography collection, the sample was silylated and analyzed by gas chromatography-negative ion chemical ionization-mass spectrometry-selected ion monitoring at m/z 372. The resulting chromatograms were remarkably clean and trans, anti-PheT was readily detected in all human urine samples. Levels of trans, anti-PheT were 791 +/- 363 pmol/mg creatinine (n = 20) in psoriasis patients treated with a PAH-containing ointment, 25.7 +/- 16.8 pmol/mg creatinine (n = 32) in coke oven workers exposed to PAH, 4.58 +/- 2.95 pmol/mg creatinine (n = 31) in smokers, and 1.51 +/- 1.15 pmol/mg creatinine (n = 30) in nonsmokers. Levels of trans, anti-PheT correlated with levels of 1-hydroxypyrene in the urine of coke oven workers, smokers, and nonsmokers. Thus, trans, anti-PheT appears to be an excellent biomarker of PAH uptake. Levels of trans, anti-PheT were 8,000-19,000 times higher than those of the corresponding metabolite of benzo[a]pyrene. The results of this study demonstrate that trans, anti-PheT can be detected in human urine. We propose that measurement of this metabolite of phenanthrene may be important as part of a carcinogen metabolite-phenotyping approach to determine individual response to PAH exposure.
- Published
- 2003
46. Null association between frequency of cured meat consumption and methylvaline and ethylvaline hemoglobin adduct levels: the N-nitroso brain cancer hypothesis.
- Author
-
Gurney JG, Chen M, Skluzacek MC, Kasum CM, Carmella SG, Villalta PW, and Hecht SS
- Subjects
- Adult, Biomarkers analysis, Cooking, Diet, Dose-Response Relationship, Drug, Humans, Valine blood, Valine chemistry, Brain Neoplasms etiology, DNA Adducts, Hemoglobins chemistry, Meat, Nitrosourea Compounds adverse effects, Valine analogs & derivatives
- Published
- 2002
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