Supplemental data from Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers

Yuan, Jian-Min; Stepanov, Irina; Murphy, Sharon E.; Wang, Renwei; Allen, Sharon; Jensen, Joni; Strayer, Lori; Adams-Haduch, Jennifer; Upadhyaya, Pramod; Le, Chap; Kurzer, Mindy S.; Nelson, Heather H.; Yu, Mimi C.; Hatsukami, Dorothy; Hecht, Stephen S.

doi:10.1158/1940-6207.22534253.v1

Supplemental data from Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers

https://doi.org/10.1158/1940-6207.22534253

journal contribution

posted on 2023-04-03, 22:08 authored by Jian-Min Yuan, Irina Stepanov, Sharon E. Murphy, Renwei Wang, Sharon Allen, Joni Jensen, Lori Strayer, Jennifer Adams-Haduch, Pramod Upadhyaya, Chap Le, Mindy S. Kurzer, Heather H. Nelson, Mimi C. Yu, Dorothy Hatsukami, Stephen S. Hecht

<p>Table S1. Number of [pyridine-D4]NNK cigarettes smoked per day by study participants by treatment sequence groups and treatment period, The PEITC Intervention Study 2008-2013 Table S2. Spearman correlation coefficients between number of cigarettes per day and urinary metabolites of nicotine, NNK, [pyridine-D4]NNK, and PGEM and 8-iso-PGF2α at the end of smoking adaption period (visit 2), The PEITC Intervention Study 2008-2013 Table S3. Urinary Levels of Total ITC and PEITC-NAC by treatment sequence groups and treatment period, The PEITC Intervention Study 2008-2013 Table S4. Geometric means of urinary [pyridine-D4]NNK metabolites by study period and treatment sequence assignment, The PEITC Intervention Study 2008-2013 Table S5. Mean level of urinary levels of PEITC-NAC and total ITC during PEITC treatment by glutathione-S-transferase (GST) genotypes, The PEITC Intervention Study 2008-2013 Table S6. Urinary levels of NNK and nicotine metabolites by PEITC treatment, The PEITC Intervention Study 2008-2013 Figure S1. Overview of the metabolism of [pyridine-D4]NNK and [pyridine-D4]NNAL leading to DNA adducts and urinary metabolites. Figure S2. Overview of the study design for the PEITC trial.</p>

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DOI - Is supplement to Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers

ARTICLE ABSTRACT

2-Phenethyl isothiocyanate (PEITC), a natural product found as a conjugate in watercress and other cruciferous vegetables, is an inhibitor of the metabolic activation and lung carcinogenicity of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats and A/J mice. We carried out a clinical trial to determine whether PEITC also inhibits the metabolic activation of NNK in smokers. Cigarette smokers were recruited and asked to smoke cigarettes containing deuterium-labeled [pyridine-D4]NNK for an acclimation period of at least 1 week. Then subjects were randomly assigned to one of two arms: PEITC followed by placebo, or placebo followed by PEITC. During the 1-week treatment period, each subject took PEITC (10 mg in 1 mL of olive oil, 4 times per day). There was a 1-week washout period between the PEITC and placebo periods. The NNK metabolic activation ratio [pyridine-D4]hydroxy acid/total [pyridine-D4]NNAL was measured in urine samples to test the hypothesis that PEITC treatment modified NNK metabolism. Eighty-two smokers completed the study and were included in the analysis. Overall, the NNK metabolic activation ratio was reduced by 7.7% with PEITC treatment (P = 0.023). The results of this trial, while modest in effect size, provide a basis for further investigation of PEITC as an inhibitor of lung carcinogenesis by NNK in smokers. Cancer Prev Res; 9(5); 396–405. ©2016 AACR.