beta-Carotene reduces bleomycin-induced genetic damage in human lymphocytes.
We had previously shown in a human feeding study that ingestion of tomato and carrot juices decreases DNA breaks and oxidized pyrimidine bases in peripheral lymphocytes and enhances expression of glutathione S-transferase (GST) in a subpopulation of the volunteers. The aim of this study was to determine how the major carotenoids of these juices (beta-carotene or lycopene) could contribute to the observed antigenotoxicity. Physiological concentrations (2 microM) of water-soluble beta-carotene and lycopene were incubated for 18-24 h with lymphocytes and then treated with bleomycin or H(2)O(2). Strand breaks, oxidized DNA bases, and persistence of damage (DNA repair) were measured by single-cell microgelelectrophoresis. GST-protein (GSTP1) was determined using an immunoassay and by measuring enzyme activity. HPLC analysis showed that beta-carotene was taken up by the cells after 24 h, and this was associated with a reduction of bleomycin-induced damage (29.11 +/- 1.86% tail intensity without versus 21.54 +/- 2.36% with beta-carotene). Lycopene was ineffective. The carotenoids did not modulate repair of bleomycin- and H(2)O(2)-induced damage and did not alter levels of oxidized pyrimidine bases nor GST expression. The results indicate that beta-carotene can enter the cell and protect against strand breaks but not against oxidized DNA bases. Therefore, beta-carotene accounts for only part of the protection observed in vivo with carotenoid-rich vegetable juices.
Glei
Michael
M
Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 25, Jena, D-07743, Germany.
Liegibel
Ute Monika
UM
Ebert
Miriam Nannette
MN
Böhm
Volker
V
Pool-Zobel
Beatrice Louise
BL
D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001761:Bleomycin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry / Q000201:enzymology; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D007527:Isoenzymes; D019207:beta Carotene; D001761:Bleomycin; D006861:Hydrogen Peroxide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase