| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1992 Oxford University Press
research-article |
Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobiotic-metabolizing enzymes and nitrosamine metabolism in rats
Laboratory for Cancer Research, College of Pharmacy, Rutgers University Piscataway, New Jersey 08855, USA
1To whom all correspondence should be addressed
Phenethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables, has been shown to inhibit chemical carcinogenesis, possibly due to its ability to block the activation or to enhance the detoxification of chemical carcinogens. The present study was conducted to elucidate the biochemical mechanisms involved by characterizing the effects of PEITC on phase I and phase II xenobiotic-metabolizing enzymes. A single dose of PEITC to F344 rats (1 mmol/kg) decreased the liver N-nitrosodimethylamine demethylase (NDMAd) activity (mainly due to P450 2E1) by 80% at 2 h and the activity of NDMAd remained decreased by 40% at 48 h after treatment. The liver pentoxyresorufin O-dealkylase (PROD) activity and P450 2B1 protein level were elevated 10- and 7-fold at 24 h after treatment respectively. The liver microsomal ethoxyresorufin O-dealkylase (EROD) (mainly due to P450 1A) and erythromycin N-demethylase (mainly due to P450 3A) activities were decreased at 2–12 h after treatment and recovered afterwards. The lung microsomal PROD and EROD activities were not significantly affected; whereas, the nasal microsomal PROD and EROD activities were decreased by 40–50%. After a treatment with PEITC, the rates of oxidative metabolism of 4-(methynitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were decreased in liver microsomes by 40–60% at 2 h and recovered gradually; the rates in lung microsomes were markedly decreased by 60–70% at 2 h and remained at the decreased level at 24 h; and the rates in nasal mucosa microsomes were decreased gradually with the lowest activities observed at 18 h (50%) followed by a gradual recovery. Furthermore, the treatment with PEITC resulted in a maximal 5-fold increase of NAD(P)H:quinone oxidoreductase and 1.5-fold increase of glutathione S-transferase activities in the liver, but the activities of these two enzymes were not significantly affected in the lung and nasal mucosa. The sulfotransferase activity in the liver was decreased by 32–48% at 24–48 h after treatment; the nasal
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Epplein, L. R. Wilkens, M. Tiirikainen, M. Dyba, F.-L. Chung, M. T. Goodman, S. P. Murphy, B. E. Henderson, L. N. Kolonel, and L. Le Marchand Urinary Isothiocyanates; Glutathione S-Transferase M1, T1, and P1 Polymorphisms; and Risk of Colorectal Cancer: The Multiethnic Cohort Study Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 314 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Wallig, K. M. Heinz-Taheny, D. L. Epps, and T. Gossman Synergy among Phytochemicals within Crucifers: Does It Translate into Chemoprotection? J. Nutr., December 1, 2005; 135(12): 2972S - 2977S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Conaway, C.-X. Wang, B. Pittman, Y.-M. Yang, J. E. Schwartz, D. Tian, E. J. McIntee, S. S. Hecht, and F.-L. Chung Phenethyl Isothiocyanate and Sulforaphane and their N-Acetylcysteine Conjugates Inhibit Malignant Progression of Lung Adenomas Induced by Tobacco Carcinogens in A/J Mice Cancer Res., September 15, 2005; 65(18): 8548 - 8557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mori, A. Koide, K. Tatematsu, S. Sugie, and H. Mori Effects of {alpha}-naphthyl isothiocyanate and a heterocyclic amine, PhIP, on cytochrome P-450, mutagenic activation of various carcinogens and glucuronidation in rat liver Mutagenesis, January 1, 2005; 20(1): 15 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Tseng, E. A. Scott-Ramsay, and M. E. Morris Dietary Organic Isothiocyanates Are Cytotoxic in Human Breast Cancer MCF-7 and Mammary Epithelial MCF-12A Cell Lines Experimental Biology and Medicine, September 1, 2004; 229(8): 835 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hu, V. Hebbar, B.-R. Kim, C. Chen, B. Winnik, B. Buckley, P. Soteropoulos, P. Tolias, R. P. Hart, and A.-N. T. Kong In Vivo Pharmacokinetics and Regulation of Gene Expression Profiles by Isothiocyanate Sulforaphane in the Rat J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 263 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-S. Keck and J. W. Finley Cruciferous Vegetables: Cancer Protective Mechanisms of Glucosinolate Hydrolysis Products and Selenium Integr Cancer Ther, March 1, 2004; 3(1): 5 - 12. [Abstract] [PDF]
|
|
|
|
|
|
A. H. Conney Enzyme Induction and Dietary Chemicals as Approaches to Cancer Chemoprevention: The Seventh DeWitt S. Goodman Lecture Cancer Res., November 1, 2003; 63(21): 7005 - 7031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. W.Y. Lui, A. L. Wentzel, D. Xiao, K. L. Lew, S. V. Singh, and J. R. Grandis Requirement of a carbon spacer in benzyl isothiocyanate-mediated cytotoxicity and MAPK activation in head and neck squamous cell carcinoma Carcinogenesis, October 1, 2003; 24(10): 1705 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Boysen, P. M.J. Kenney, P. Upadhyaya, M. Wang, and S. S. Hecht Effects of benzyl isothiocyanate and 2-phenethyl isothiocyanate on benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism in F-344 rats Carcinogenesis, March 1, 2003; 24(3): 517 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Zhao, A. Seow, E. J. D. Lee, W.-T. Poh, M. Teh, P. Eng, Y.-T. Wang, W.-C. Tan, M. C. Yu, and H.-P. Lee Dietary Isothiocyanates, Glutathione S-transferase -M1, -T1 Polymorphisms and Lung Cancer Risk among Chinese Women in Singapore Cancer Epidemiol. Biomarkers Prev., October 1, 2001; 10(10): 1063 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Kleiner, S. V. Vulimiri, L. Miller, W. H. Johnson Jr, C. P. Whitman, and J. DiGiovanni Oral administration of naturally occurring coumarins leads to altered phase I and II enzyme activities and reduced DNA adduct formation by polycyclic aromatic hydrocarbons in various tissues of SENCAR mice Carcinogenesis, January 1, 2001; 22(1): 73 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Goosen, D. E. Mills, and P. F. Hollenberg Effects of Benzyl Isothiocyanate on Rat and Human Cytochromes P450: Identification of Metabolites Formed by P450 2B1 J. Pharmacol. Exp. Ther., January 1, 2001; 296(1): 198 - 206. [Abstract] [Full Text]
|
|
|
|
|
|
P. Rose, K. Faulkner, G. Williamson, and R. Mithen 7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes Carcinogenesis, November 1, 2000; 21(11): 1983 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Hecht, S. G. Carmella, and S. E. Murphy Effects of Watercress Consumption on Urinary Metabolites of Nicotine in Smokers Cancer Epidemiol. Biomarkers Prev., October 1, 1999; 8(10): 907 - 913. [Abstract] [Full Text]
|
|
|
|
|
|
S. S. Hecht Chemoprevention of Cancer by Isothiocyanates, Modifiers of Carcinogen Metabolism J. Nutr., March 1, 1999; 129(3): 768 - 768. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. C. Conaway, D. Jiao, T. Kohri, L. Liebes, and F.-L. Chung Disposition and Pharmacokinetics of Phenethyl Isothiocyanate and 6-Phenylhexyl Isothiocyanate in F344 Rats Drug Metab. Dispos., January 1, 1999; 27(1): 13 - 20. [Abstract] [Full Text]
|
|