AQUEOUS EXTRACTS OF SELENIUM-FERTILIZED BROCCOLI INCREASE SELENOPROTEIN ACTIVITY AND INHIBIT DNA SINGLE-STRAND BREAKS, BUT DECREASE THE ACTIVITY OF QUINONE REDUCTASE IN HEPA 1C1C7 CELLS

Authors: KECK, ANNA-SIGRID - UNIV OF ILLINOIS; Finley, John

Submitted to: Food and Chemical Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/10/2005
Publication Date: 5/1/2006
Citation: Keck, A., Finley, J.W. 2006. Aqueous extracts of selenium-fertilized broccoli increase selenoprotein activity and inhibit DNA single-strand breaks, but decrease the activity of quinone reductase in Hepa 1c1c7 cells. Food and Chemical Toxicology. 44:695-703.

Interpretive Summary: Consumption of selenium (Se) and/or broccoli may decrease the risk of several important cancers. Compounds in broccoli called glucosinolates increase the activity of enzymes that excrete carcinogens from the body, whereas Se is needed for the production of proteins that function as antioxidants. This study has examined whether selenium and/or other compounds from broccoli function as antioxidants and reduce damage to DNA, an event that may initiate cancer. Selenium and sulforaphane a glucosinolate from broccoli, both protected against DNA strand breaks, however, selenium was the most effective compound, but broccoli enriched in selenium was more effective than either pure compound. These results suggest that some of the previously reported anti-cancer activity of Se, SF and selenized broccoli may be by blocking cancer initiation through prevention of DNA single-strand breaks.

Technical Abstract: Depending on growth conditions, broccoli may be enriched in the isothiocyanate sulforaphane (SF) and/or the mineral selenium (Se); both compounds may play an important role in the reduction of intracellular oxidative stress. Sulforaphane up-regulates transcription of Phase II detoxification proteins (e.g. quinone reductase [QR]), whereas Se is needed for the production of thioredoxin reductase (TR) and glutathione peroxidase-1 (GPx1), both of which exhibit antioxidant activity. The objective of the present study was to determine whether the fertilization of broccoli with Se increases the antioxidant ability of broccoli. Hydrogen peroxide-induced DNA single-strand breaks (measured by single cell electrophoresis, Comet assay) and activity of antioxidant enzymes (GPx, TR and quinone reductase) were measured in mouse hepatoma cells (Hepa 1c1c7 cells) treated with purified SF, Se (as selenite) or extracts of selenized broccoli. When supplied separately as chemically pure substances, selenite was more effective than SF for reduction of single-strand breaks. Se-fertilized broccoli extracts were the most effective for reduction of single-strand breaks, and extracts that contained 0.71 µM Se and 0.08 µM SF inhibited 94% of DNA single-strand breaks. A significant positive association (R=0.81, p=0.009) between GPx1 activity and inhibition of DNA single-strand breaks as well as a 24h lag time between addition of Se, SF or broccoli extract and inhibition of single-strand breaks suggests that some of the antioxidant protection is mediated through selenoproteins. Conversely, fertilization of broccoli with Se decreased the ability of broccoli extract to induce QR activity. These results demonstrate that Se and Sf, alone or as a component of broccoli, may help decrease oxidative stress. They further suggest that Se is the most important for decreasing oxidative stress, but maximizing the Se content of broccoli also may compromise its ability to induce phase II detoxification proteins.