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Cancer Prev Res (Phila)

Title:		"2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke"
Author(s):		Yuan JM; Murphy SE; Stepanov I; Wang R; Carmella SG; Nelson HH; Hatsukami D; Hecht SS;
Address:		"University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania. yuanj@upmc.edu. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Department of Biochemistry, Molecular Biology and BioPhysics, University of Minnesota, Minneapolis, Minnesota. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota"
Journal Title:		Cancer Prev Res (Phila)
Year:		2016
Volume:		20160420
Issue:		7
Page Number:		598 - 606
DOI:		10.1158/1940-6207.CAPR-16-0032
ISSN/ISBN:		1940-6215 (Electronic) 1940-6207 (Print) 1940-6215 (Linking)
Abstract:		"Cigarette smoke contains relatively large quantities of volatile organic toxicants or carcinogens such as benzene, acrolein, and crotonaldehyde. Among their detoxification products are mercapturic acids formed from glutathione conjugation, catalyzed in part by glutathione S-transferases (GST). A randomized phase II clinical trial with a crossover design was conducted to evaluate the effect of 2-phenethyl isothiocyanate (PEITC), a natural product formed from gluconasturtiin in certain cruciferous vegetables, on the detoxification of benzene, acrolein, and crotonaldehyde in 82 cigarette smokers. Urinary mercapturic acids of benzene, acrolein, and crotonaldehyde at baseline and during treatment were quantified. Overall, oral PEITC supplementation increased the mercapturic acid formed from benzene by 24.6% (P = 0.002) and acrolein by 15.1% (P = 0.005), but had no effect on crotonaldehyde. A remarkably stronger effect was observed among subjects with the null genotype of both GSTM1 and GSTT1: in these individuals, PEITC increased the detoxification metabolite of benzene by 95.4% (P < 0.001), of acrolein by 32.7% (P = 0.034), and of crotonaldehyde by 29.8% (P = 0.006). In contrast, PEITC had no effect on these mercapturic acids in smokers possessing both genes. PEITC had no effect on the urinary oxidative stress biomarker 8-iso-prostaglandin F2alpha or the inflammation biomarker prostaglandin E2 metabolite. This trial demonstrates an important role of PEITC in detoxification of environmental carcinogens and toxicants which also occur in cigarette smoke. The selective effect of PEITC on detoxification in subjects lacking both GSTM1 and GSTT1 genes supports the epidemiologic findings of stronger protection by dietary isothiocyanates against the development of lung cancer in such individuals. Cancer Prev Res; 9(7); 598-606. (c)2016 AACR"
Keywords:		"Acrolein/metabolism Adult Aldehydes/metabolism Benzene/metabolism Carcinogens/*metabolism Cross-Over Studies Enzyme Inhibitors/*therapeutic use Female Glutathione Transferase/genetics Humans Inactivation, Metabolic/*drug effects/genetics Isothiocyanates/*;"
Notes:		"MedlineYuan, Jian-Min Murphy, Sharon E Stepanov, Irina Wang, Renwei Carmella, Steven G Nelson, Heather H Hatsukami, Dorothy Hecht, Stephen S eng P30 CA077598/CA/NCI NIH HHS/ R01 CA122244/CA/NCI NIH HHS/ Clinical Trial, Phase II Randomized Controlled Trial 2016/04/22 Cancer Prev Res (Phila). 2016 Jul; 9(7):598-606. doi: 10.1158/1940-6207.CAPR-16-0032. Epub 2016 Apr 20"