Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium-enriched garlic in rats.
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.
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Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. cip@sc3101.med.buffalo.edu
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D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D015331:Cohort Studies; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism; D004032:Diet; D005260:Female; D005737:Garlic; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000378:metabolism*; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D015262:Xenobiotics / Q000378:metabolism
D002273:Carcinogens; D018736:DNA Adducts; D015262:Xenobiotics; D015127:9,10-Dimethyl-1,2-benzanthracene; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D012643:Selenium