|
ISS
820 East 20th Street
Cookeville, TN 38501 USA
931 526 1106
Bob@sproutnet.com
中文版
En espaņol
| |
Dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and
2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA), two naturally occurring
benzoxazinones contained in sprouts of Gramineae are potent aneugens in
human-derived liver cells (HepG2).
Cancer Lett. 2006 Apr 24; [Epub ahead of print]
Buchmann CA, Nersesyan A, Kopp B, Schauberger D, Darroudi F, Grummt T, Krupitza
G, Kundi M, Schulte-Hermann R, Knasmueller S.
Division Institute of Cancer Research, Department of Medicine I, Medical
University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
Benzoxazinoids (BAs) are toxic constituents of sprouts of Gramineae such as
wheat, maize and rye and are part of the plant defence system against pests. In
the last years, sprouts have been increasingly consumed as health foods and are
also used for the production of dietary supplements. In the present study we
investigated the mutagenic activities of the two most abundant BAs, namely
2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and
2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) in the Salmonella/microsome assay and
additionally, in micronucleus (MN) assay and single cell gel electrophoresis (SCGE)
assay in a human-derived liver cell line (HepG2). DIBOA caused significant
induction of his(+) revertants in all three strains in the range between 0.02
and 0.50mg/plate; the highest activity was observed in TA100 (fivefold increase
over the background at the highest dose level). The effect in YG1024 (a
derivative of TA98 with increased acetyltransferase activity) was only slightly
higher than the effect in the parental strain indicating that acetylation plays
no crucial role in the activation of this BA. DIMBOA was in general less active
and a positive result was only seen in the base substitution strain (TA100).
Addition of rat liver homogenate (S9-mix) led to a significant (ca. twofold)
increase of the mutagenic activities of both BAs. In SCGE assays with HepG2
cells consistently negative results were obtained with both compounds whereas in
MN assays significant dose dependent effects were observed under similar
experimental conditions. DIMBOA caused significant effects already at
concentrations >/=1muM; at the highest dose (20muM) the MN frequency was
sevenfold higher than the background level. DIBOA caused weaker effects and was
positive at doses >/=2.5muM, the maximal induction (twofold over background) was
observed with 20muM. Overall, DIMBOA was ca. 30-fold more active as DIBOA.
Subsequent experiments with pancentromeric probes showed that >80% of the MN
induced at the highest doses gave a centromere positive signal indicating that
both BAs are aneugenic. This is an interesting observation as it is assumed that
aneuploidy is a key event in cancer induction and at present no other aneugenic
plant-derived substances of dietary relevance are known.
|
