Gene expression profiling in Caco-2 human colon cells exposed to TCDD, benzo[a]pyrene, and natural Ah receptor agonists from cruciferous vegetables and citrus fruits.
Cruciferous vegetables and citrus fruits are reported to possess health-beneficial properties, but also have been shown to contain natural aryl hydrocarbon receptor (AhR) agonists (NAhRAs). Binding to the AhR is widely assumed to activate the main pathway by which dioxins, like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exert their toxicity. To establish whether or not activation of the AhR pathway by NAhRAs and dioxin-like substances results in similar cellular responses, gene expression profiles induced in Caco-2 cells were studied using microarray analysis. Cells were exposed to indolo[3,2-b]carbazole (ICZ), an acid reaction product from cruciferous vegetables, and to extracts of citrus pulp and grapefruit juice. Gene expression profiles induced by these NAhRAs were compared to those of the xenobiotic AhR agonists TCDD and benzo[a]pyrene (B[a]P). Over 20 genes were found more than 1.5 times up- or down-regulated by TCDD, and the expression of most of these genes was modulated in the same direction and to a similar extent by B[a]P and the NAhRAs. Results were confirmed by RT-PCR, and many of these genes may be involved in dioxin-related toxic effects. In conclusion, this in vitro study showed similar effects induced by NAhRAs, TCDD and B[a]P at the transcriptome level in a human intestinal cell line.
Department of Health Risk Analysis and Toxicology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
W J
WJ
de Waard
J M M J G
JM
Aarts
A A C M
AA
Peijnenburg
H
H
Baykus
E
E
Talsma
A
A
Punt
T M C M
TM
de Kok
F J
FJ
van Schooten
L A P
LA
Hoogenboom
D001564:Benzo(a)pyrene / Q000633:toxicity*; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D002957:Citrus / Q000737:chemistry*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000737:chemistry; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014675:Vegetables / Q000737:chemistry*; D015262:Xenobiotics / Q000633:toxicity
D018076:DNA, Complementary; D004785:Environmental Pollutants; D010936:Plant Extracts; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; D001564:Benzo(a)pyrene; D012313:RNA; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1