title: Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers.
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.
authors.affiliation: Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Irina
authors.initials: I
authors.lastname: Stepanov
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Department of Biochemistry, Molecular Biology and BioPhysics, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Murphy
authors.affiliation: Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Renwei
authors.initials: R
authors.lastname: Wang
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Sharon
authors.initials: S
authors.lastname: Allen
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Joni
authors.initials: J
authors.lastname: Jensen
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Lori
authors.initials: L
authors.lastname: Strayer
authors.affiliation: Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adams-Haduch
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Pramod
authors.initials: P
authors.lastname: Upadhyaya
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Chap
authors.initials: C
authors.lastname: Le
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, Minnesota.
authors.forename: Mindy S
authors.initials: MS
authors.lastname: Kurzer
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Nelson
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California.
authors.forename: Mimi C
authors.initials: MC
authors.lastname: Yu
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hatsukami
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. hecht002@umn.edu.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
mesh_terms: D065767:Activation, Metabolic / Q000187:drug effects; D000328:Adult; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000032:analysis*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009602:Nitrosamines / Q000652:urine*; D012907:Smoking / Q000652:urine*
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D017879:Isothiocyanates; D009602:Nitrosamines; C058305:phenethyl isothiocyanate; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone