Indole-3-carbinol: Anticarcinogen or tumor promoter in brassica vegetables?

Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822, USA.
Chemico-Biological Interactions (Impact Factor: 2.98). 04/1998; 110(1-2):1-5. DOI: 10.1016/S0009-2797(97)00115-4
Source: PubMed

ABSTRACT Indole-3-carbinol (I3C) is one of several compounds in brassica vegetables that demonstrate anticarcinogenic effects in experimental animals. A review of Medline and CancerLit databases indicated that interest in I3C, as a cancer chemopreventive agent, has increased significantly in the past 5-10 years. Whereas most studies report inhibitory or protective effects of I3C in vivo, a few provide clear evidence for promotion or enhancement of carcinogenesis, depending upon the initiator, exposure protocol and species. In the absence of detailed information on the inhibitory and in particular, promotional mechanisms, it would seem advisable to proceed with caution before including I3C in extensive human clinical trials.

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    • "This is in agreement with many studies reporting beneficial effects of vegetables and fruit consumption [15] [16]. Nevertheless, some animal experiments with I3C showed an increase in tumor formation after initiation with a carcinogen [17] and ICZ showed a TCDD-like inhibition of gap junction intercellular communication in vitro, indicative of a tumor promotive effect [18]. Also epidemiological studies are inconsistent as to the overall healthy effects of foods containing NAhRAs or vegetables and fruit in general [19] [20] [21]. "
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    ABSTRACT: Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA.Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX® showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine.
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    • "could be prodrugs for cancer therapy (Chen et al., 2001; Dashwood, 1998; Edwards et al., 1999; Folkes and Wardman, 2001; Greco et al., 2002; Hong et al., 2002; Leong et al., 2001; Rossiter, 2002; Stresser et al., 1995; Wardman, 2002). BNOA has been categorised in the chemical group that demonstrated slightly acute toxicity by the Pesticide Action Network (PAN, 2009) but there are no data on its long-term effects in this site. "
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    ABSTRACT: In this study, the mutagenic and recombinogenic effects of indole-3-acetic acid (IAA), a plant growth regulator naturally synthesized in plants but produced synthetically, and β-naphthoxyacetic acid (BNOA), a synthetic plant growth regulator widely used in agricultural regions, were investigated using the somatic mutation and recombination test (SMART) in Drosophila wings. The effect of the same plant growth regulators against the proliferation and viability of a human immortalized embryonic kidney HEK293 cells which is at the early stage of carcinogenesis were also examined with MTT and trypan-blue exclusion assays. For the SMART assay, two different crosses were used: a standard and a high-bioactivation (HB) cross, involving the flare-3 and the multiple wing hairs markers. The HB cross involved flies characterized by an increased cytochrome P-450-dependent bioactivation capacity, which permits the more efficient biotransformation of promutagens and procarcinogens. In both crosses, the wings of the two types of progeny, inversion-free marker heterozygotes and balancer heterozygotes, were analyzed. The results show that IAA and BNOA are not mutagenic or recombinogenic in the wing cells of Drosophila. Furthermore, neither plant growth regulator affected the proliferation rate of HEK293 cells; however, both of them induced cell death at high concentrations.
    Toxicology and Industrial Health 04/2011; 27(9):840-8. DOI:10.1177/0748233711399314 · 1.71 Impact Factor
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    • "CYP1A2 induction by concentrated food additives , also can initiate dioxin - like toxic pathways , especially when slow processes like tumor promotion are involved . Besides tumor suppressing capacity , high doses of NAhRAs given to laboratory animals have sometimes also shown tumor promoting capacity ( Dashwood 1998 ) , and the accumulation effect of persistent fat - soluble xenobiotic AhR agonists could be mimicked by constant or regular NAhRA exposure . "
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    ABSTRACT: The aryl hydrocarbon receptor (AhR) receives much attention for its role in the toxicity of dioxins and dioxin-like polychlorinated biphenyls. However, many other compounds have also been reported to bind and activate AhR, of which natural food components are of special interest from a human health perspective. Using the dioxin receptor-chemical-activated luciferase gene expression (DR CALUX) bioassay, extracts from many food items frequently consumed in the Netherlands were screened to estimate the intake of natural AhR agonists (NAhRAs). Using the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as standard, it was estimated that the daily intake of NAhRAs might be considerably higher than the reported intake of dioxins and dioxin-like polychlorinated biphenyls. Potatoes, cruciferous vegetables, bread, hamburgers, and grapefruit juice contained most NAhRAs. Food preparation and acid treatment can show a significant effect on AhR activation. The interaction of natural and xenobiotic AhR agonists should be taken into account when performing risk-benefit analysis of both types of compounds.
    Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment 07/2008; 25(6):779-87. DOI:10.1080/02652030701798880 · 2.34 Impact Factor
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