Protective effects of Brussels sprouts towards B[a]P-induced DNA damage: a model study with the single-cell gel electrophoresis (SCGE)/Hep G2 assay.
The aim of this study was to investigate the chemoprotective effects of Brussels sprouts juice towards benzo[a]pyrene (B(a)P)-induced DNA damage in the single-cell gel electrophoresis (SCGE)/Hep G2 test system. This assay combines the advantages of the SCGE assay with that of the use of human-derived cells possessing inducible phase I and phase II enzymes. Co-treatment of Hep G2 cells with small amounts of Brussels sprouts juice (0.25-2.0 microl/ml) and B(a)P reduced the genotoxic effect of the latter in a dose-dependent manner. Contrary to the results with the crude juice, unexpected synergistic effects were observed with allyl isothiocyanate (AITC, 1.0-6.0 microM), a breakdown product of sinigrin, which is the most abundant glucosinolate in Brussels sprouts. Although these concentrations of AITC did not cause DNA damage per se, at higher concentrations (> or =25 microM), the compound caused a pronounced dose-dependent DNA damage by itself. Mechanistic studies showed that Brussels sprouts juice causes induction of activities of ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) at dose levels which were protective towards B(a)P. In combined treatment experiments with (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE, 5.0 microM), the main genotoxic metabolite of B(a)P, and Brussels sprouts juice, only weak protection was found indicating that the mechanism of chemoprotection of Brussels sprouts is not mediated through inactivation of this metabolite. In conclusion, our findings show that Brussels sprouts are highly protective against B(a)P-induced DNA damage in human-derived cells.
Laky
B
B
Insitute of Cancer Research, University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.
Knasmüller
S
S
Gminski
R
R
Mersch-Sundermann
V
V
Scharf
G
G
Verkerk
R
R
Freywald
C
C
Uhl
M
M
Kassie
F
F
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001937:Brassica / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000517:prevention & control; D009152:Mutagenicity Tests; D010936:Plant Extracts / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017879:Isothiocyanates; D010936:Plant Extracts; D001564:Benzo(a)pyrene; C004471:allyl isothiocyanate; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase