2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke.
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 F2α 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. ©2016 AACR.
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania. yuanj@upmc.edu.
Jian-Min
JM
Yuan
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Department of Biochemistry, Molecular Biology and BioPhysics, University of Minnesota, Minneapolis, Minnesota.
Sharon E
SE
Murphy
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Irina
I
Stepanov
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Renwei
R
Wang
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Steven G
SG
Carmella
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
Heather H
HH
Nelson
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Dorothy
D
Hatsukami
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Stephen S
SS
Hecht
D000171:Acrolein / Q000378:metabolism; D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D001554:Benzene / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects* / Q000235:genetics; D017879:Isothiocyanates / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects / Q000188:drug therapy* / Q000378:metabolism; D055549:Volatile Organic Compounds / Q000009:adverse effects / Q000378:metabolism; D062789:Tobacco Products
D000171:Acrolein; D000447:Aldehydes; D001554:Benzene; D002273:Carcinogens; D004791:Enzyme Inhibitors; D005982:Glutathione Transferase; D017879:Isothiocyanates; D012906:Smoke; D055549:Volatile Organic Compounds; C058305:phenethyl isothiocyanate; C012796:2-butenal; C413545:glutathione S-transferase T1