Effect of diallyl sulfide, a naturally occurring anti-carcinogen, on glutathione-dependent detoxification enzymes of female CD-1 mouse tissues.
The present studies were undertaken to elucidate the mechanism(s) of the anti-neoplastic effect of diallyl sulfide (allyl sulfide, DAS), a naturally occurring organosulfide abundant in vegetables of the Allium genus, against benzo[a]pyrene (B[a]P)-induced carcinogenesis in the mouse. DAS treatment caused a significant increase in glutathione S-transferase (GST) activity, an enzyme system responsible for detoxification of a variety of electrophilic xenobiotics including several harmful B[a]P metabolites, of mouse stomach in a dose-dependent manner. This activity in the stomach of mice treated with 25, 50 and 75 mumol DAS was higher by 1.13-, 1.20- and 1.58-fold, respectively, when compared to the control. Purification and quantitation of GST from equal amounts (1.2 g) of control and 50 mumol DAS-treated mice stomach tissues demonstrated that elevation in activity occurred as a result of increased de novo synthesis of the enzyme protein. DAS treatment also resulted in increased pulmonary GST activity, but not in a dose-dependent fashion. On the other hand, treatment of mice with DAS did not alter hepatic GST activity. Interestingly, a small but statistically significant (P less than or equal to 0.05) reduction in kidney GST activity was observed in mice treated with 50 or 75 mumol DAS, as compared to the control. The effect of DAS treatment was also assessed on glutathione (GSH) peroxidase activity, another GSH-dependent detoxification enzyme, in mouse tissues. Treatment of animals with 25, 50 and 75 mumol DAS increased stomach GSH peroxidase activity by 1.64-, 1.93- and 2.52-fold, respectively, over the control. This enzyme activity in the lungs of mice treated with 25, 50 and 75 mumol DAS was higher by 1.44-, 1.54- and 1.21-fold, respectively, when compared to the control. On the other hand, GSH peroxidase activity in liver and kidney was unchanged by DAS treatment. These results suggest that DAS and perhaps other naturally occurring organosulfur compounds may exert an anti-neoplastic effect by modulating GSH-dependent detoxification enzymes.
Gudi
V A
VA
Department of Oncology, University of Miami School of Medicine, FL 33136.
Singh
S V
SV
D000498:Allyl Compounds; D000818:Animals; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005737:Garlic; D005979:Glutathione Peroxidase / Q000096:biosynthesis*; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000302:isolation & purification; D008658:Inactivation, Metabolic; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D010938:Plant Oils / Q000494:pharmacology*; D010946:Plants, Medicinal; D013270:Stomach / Q000187:drug effects / Q000201:enzymology; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D010938:Plant Oils; D013440:Sulfides; D001564:Benzo(a)pyrene; C038491:allyl sulfide; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase