2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke.

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 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.

• Authors: Jian-Min Yuan, Sharon E Murphy, Irina Stepanov, Renwei Wang, Steven G Carmella, Heather H Nelson, Dorothy Hatsukami, Stephen S Hecht
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 9 Issue 7 Pg. 598-606 (Jul 2016) ISSN: 1940-6215 [Electronic] United States
• PMID: 27099270 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Aldehydes
• Carcinogens
• Enzyme Inhibitors
• Isothiocyanates
• Smoke
• Volatile Organic Compounds
• phenethyl isothiocyanate
• Acrolein
• 2-butenal
• glutathione S-transferase T1
• Glutathione Transferase
• glutathione S-transferase M1
• Benzene

Topics

• 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 (therapeutic use)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Smoke (adverse effects)
• Smoking (adverse effects, drug therapy, metabolism)
• Nicotiana (adverse effects, chemistry, metabolism)
• Volatile Organic Compounds (adverse effects, metabolism)