Document Detail


Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium-enriched garlic in rats.
MedLine Citation:
PMID:  9290126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous research showed that treatment with selenium-enriched garlic (Se-garlic) was able to inhibit the initiation phase of mammary carcinogenesis in the dimethyl-benz[a]anthracene (DMBA) model in rats. The present study was designed to investigate the following parameters: 1) DMBA-DNA adduct formation in liver and mammary gland, 2) urinary excretion of DMBA metabolites, 3) phase I and phase II xenobiotic-metabolizing enzymes, and 4) tissue selenium levels as a function of Se-garlic supplementation. Prior feeding with an Se-garlic-containing diet (at 3 ppm Se) for two weeks resulted in a consistent reduction of all DMBA adducts in liver and mammary gland. This was accompanied by a 40% increase in urinary excretion of DMBA metabolites over a two-day period. Several liver P-450 enzymes were examined in rats fed a diet supplemented with 1, 2, or 3 ppm Se. Compared with controls receiving 0.1 ppm Se, no significant alteration in activity was detected with respect to P-450 1A1 (responsible for DMBA activation), 1A2, 2B1, 2E1, and 3A4. In contrast, glutathione S-transferase and uridine 5'-diphosphate-glucuronyltransferase activities were elevated to a maximum of 2- to 2.5-fold in liver and kidney. As expected, there was a dose-dependent elevation of selenium concentrations in liver, kidney, mammary gland, and plasma as a function of the level of Se-garlic supplementation. Our data seem to suggest that an increased detoxification of carcinogen via the phase II conjugating enzymes might represent a mechanism of tumor suppression by Se-garlic.
Authors:
C Ip; D J Lisk
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nutrition and cancer     Volume:  28     ISSN:  0163-5581     ISO Abbreviation:  Nutr Cancer     Publication Date:  1997  
Date Detail:
Created Date:  1997-12-17     Completed Date:  1997-12-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7905040     Medline TA:  Nutr Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  184-8     Citation Subset:  IM    
Affiliation:
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. cip@sc3101.med.buffalo.edu
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MeSH Terms
Descriptor/Qualifier:
9,10-Dimethyl-1,2-benzanthracene / metabolism
Animals
Carcinogens / metabolism
Cohort Studies
Cytochrome P-450 Enzyme System / drug effects,  metabolism*
DNA Adducts / metabolism
Diet
Female
Garlic*
Glucuronosyltransferase / drug effects,  metabolism*
Glutathione Transferase / drug effects,  metabolism*
Kidney / drug effects,  enzymology,  metabolism
Liver / drug effects,  enzymology,  metabolism
Mammary Glands, Animal / drug effects,  enzymology,  metabolism
Plants, Medicinal*
Rats
Rats, Sprague-Dawley
Selenium / administration & dosage,  pharmacokinetics,  pharmacology*
Specific Pathogen-Free Organisms
Xenobiotics / metabolism
Grant Support
ID/Acronym/Agency:
CA-27706/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Carcinogens; 0/DNA Adducts; 0/Xenobiotics; 57-97-6/9,10-Dimethyl-1,2-benzanthracene; 7782-49-2/Selenium; 9035-51-2/Cytochrome P-450 Enzyme System; EC 2.4.1.17/Glucuronosyltransferase; EC 2.5.1.18/Glutathione Transferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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