Mutagenicity of plant flavonoids: Structural requirements for mutagenic activity in Salmonella typhimurium

MacGregor, James T.; Jurd, L.

doi:10.1016/0165-1161(78)90020-1

Cited by 282 publications

(100 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, depending on the concentration and hydroxyl substituent pattern, phenolic compounds can also act as pro-oxidants (Laughton et al, 1989;Yamanaka et al, 1997;Metodiewa et al, 1999). Other negative physiological effects of flavonoids (mutagenicity, genotoxicity, cytotoxicity) have also been described (MacGregor & Jurd, 1978;Brown & Dietrich, 1979;Brown, 1980;Rueff et al, 1992;Yamanaka et al, 1997;Metodiewa et al, 1999;Hodek et al, 2002). Most of these physiological effects are based on either in vitro models, cell/tissue culture studies, animal experiments or epidemiological data.…”

Section: Structure Classification Distribution Of Phenols In Plant mentioning

confidence: 99%

Reactions of Plant Phenolics with Food Proteins and Enzymes under Special Consideration of Covalent Bonds

Kröll

Rawel

Rohn

2003

FSTR

327

273

View full text Add to dashboard Cite

Secondary plant metabolites are important native food components, which are becoming more and more interesting due to their physiological effects on human beings. One of the largest groups of these compounds is represented by plant phenols. This review summarizes the structure, classification and distribution of the phenolic compounds in plant foods, their chemistry and signification with regard to food processing and -storage as well as their physiological effects. This work focuses mainly on such reactions of the phenolic substances with proteins and enzymes that lead to covalent bonds. The derivatives formed have been characterized in terms of changes in their physicochemical and structural properties. The effect on the proteolytic in vitro digestion has been also illustrated. Further aspects reported include the influence on enzyme activity and -kinetic parameters. The different aspects of the nutritional-physiological consequences of such reactions in food and body, especially considering their significance to food science and technology are discussed.

show abstract

Section: Structure Classification Distribution Of Phenols In Plant mentioning

confidence: 99%

Reactions of Plant Phenolics with Food Proteins and Enzymes under Special Consideration of Covalent Bonds

Kröll

Rawel

Rohn

2003

FSTR

327

273

View full text Add to dashboard Cite

show abstract

“…In the light of its interesting biological properties germane to anticarcinogenesis, quercetin has been subjected to a phase I clinical trial in cancer patients, with the aim to develop it as a cancer chemopreventive or antineoplastic agent (Ferry et al, 1996). With respect to potential detrimental effects on health by quercetin, it has been suggested to possess mutagenic and carcinogenic properties (MacGregor and Jurd, 1978;Dunnick and Hailey, 1992), and at high doses there were indications of toxicity in humans (Ferry et al, 1996).…”

mentioning

confidence: 99%

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

et al. 2004

View full text Add to dashboard Cite

Quercetin (3,5,7,3 0 ,4 0 -pentahydroxyflavone) is a flavone with putative ability to prevent cancer and cardiovascular diseases. Its metabolism was evaluated in rats and human. Rats received quercetin via the intravenous (i.v.) route and metabolites were isolated from the plasma, urine and bile. Analysis was by high-performance liquid chromatography and confirmation of species identity was achieved by mass spectrometry. Quercetin and isorhamnetin, the 3 0 -O-methyl analogue, were found in both the plasma and urine. In addition, several polar peaks were characterised as sulphated and glucuronidated conjugates of quercetin and isorhamnetin. Extension of the metabolism studies to a cancer patient who had received quercetin as an i.v. bolus showed that (Quercetin removed) isorhamnetin and quercetin 3 0 -O-sulphate were major plasma metabolites. As a catechol, quercetin can potentially be converted to a quinone and subsequently conjugated with glutathione (GSH). Oxidation of quercetin with mushroom tyrosinase in the presence of GSH furnished GSH conjugates of quercetin, two mono-and one bis-substituted conjugates. However, these species were not found in biomatrices in rats treated with quercetin. As cyclo-oxygenase-2 (COX-2) expression is mechanistically linked to carcinogenesis, we examined whether quercetin and its metabolites can inhibit COX-2 in a human colorectal cancer cell line (HCA-7). Isorhamnetin and its 4 0 -isomer tamarixetin were potent inhibitors, reflected in a 90% decrease in prostaglandin E-2 (PGE-2) levels, a marker of COX-2 activity. Quercetin was less effective, with a 50% decline. Quercetin 3-and 7-O-sulphate had no effect on PGE-2. The results indicate that quercetin may exert its pharmacological effects, at least in part, via its metabolites. Naturally occurring flavonoids in the diet are associated with several beneficial health effects and understanding the mechanisms underlying these effects has become the focus of much research. Quercetin (3,5,7,3 0 ,4 0 -pentahydroxyflavone, for structure see Figure 1) is a prime example of such a flavonoid. Its glycosylated form occurs in kale, French beans, broccoli, apples and especially in onions, with an abundance as high as a quarter to half a gram per kg (Hertog et al, 1992). On ingestion with the diet, quercetin glycosides are rapidly hydrolysed to generate quercetin.Epidemiological evidence links diets rich in quercetin with decreased incidence of cardiovascular and neoplastic diseases

show abstract

“…However, a serious toxicologic impediment of many flavonols, which militates against their development as cancer chemopreventive agents, is their mutagenicity as reflected by the Ames test. Quercetin at levels of typically 20 μg or more per plate (24)(25)(26) and, to a lesser extent, fisetin at ∼500 μg per plate (27), were shown to be mutagenic. There is also limited evidence for the carcinogenicity of quercetin in animals (28,29).…”

Section: Introductionmentioning

confidence: 99%

“…We also measured TMFol levels in murine tumor tissue to relate activity to the presence of pharmacologically active agent. The potential mutagenicity of TMFol was investigated in the Ames reverse mutation assay using a panel of Salmonella Typhimurium strains, in which quercetin has shown mutagenic activity (24)(25)(26)(27). Overall, the work was designed to discover safe and efficacious cancer chemopreventive agents structurally based on pharmacologically interesting plant constituents.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Colorectal Cancer Chemopreventive Efficacy and p53-Modulating Activity of 3′,4′,5′-Trimethoxyflavonol, a Quercetin Analogue

Howells

Britton

Mazzoletti

et al. 2010

Cancer Prevention Research

View full text Add to dashboard Cite

Some naturally occurring flavonols, exemplified by quercetin, seem to possess experimental cancer chemopreventive efficacy. Modulation of p53 is a mechanism thought to contribute to their activity. The hypothesis was tested that a synthetic flavonol, 3′,4′,5′-trimethoxyflavonol (TMFol), can interfere with tumor development and p53 expression in two models of colorectal carcinogenesis, Apc Min mice and human-derived HCT116 adenocarcinoma-bearing nude mice. Mice received TMFol with their diet (0.2%) from weaning to week 16 in the case of Apc Min or from either day 7 before ("TMFol early") or day 7 after ("TMFol late") tumor inoculation in HCT116 mice. The ability of TMFol to affect tumor proliferation or apoptosis, as reflected by staining for Ki-67 or cleaved caspase-3, respectively, was studied in HCT116 tumors. TMFol tumor levels were measured by high-performance liquid chromatography. Consumption of TMFol reduced small intestinal adenoma burden in Apc Min mice by 47%, compared with control mice (P < 0.002). The TMFol early regimen approximately halved HCT116 tumor size (P < 0.05), decreased tumor proliferation, and increased apoptosis, whereas the TMFol late regimen had no significant effect when compared with controls. In tumor tissues from mice, in which TMFol reduced tumor development, p53 expression was increased 3-fold in Apc Min and 1.5-fold in HCT116 tumor-bearing mice (P = 0.02). TMFol increased p53 also in cells derived from these tumors. TMFol was detected in HCT116 tumors, but levels did not correlate with tumor burden. TMFol was not mutagenic in the Ames test. The results suggest that chemical modification of the flavonol structure may generate safe and efficacious cancer chemopreventive agents. Cancer Prev Res; 3(8); 929-39. ©2010 AACR.

show abstract

Mutagenicity of plant flavonoids: Structural requirements for mutagenic activity in Salmonella typhimurium

Cited by 282 publications

References 12 publications

Reactions of Plant Phenolics with Food Proteins and Enzymes under Special Consideration of Covalent Bonds

Reactions of Plant Phenolics with Food Proteins and Enzymes under Special Consideration of Covalent Bonds

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

Preclinical Colorectal Cancer Chemopreventive Efficacy and p53-Modulating Activity of 3′,4′,5′-Trimethoxyflavonol, a Quercetin Analogue

Contact Info

Product

Resources

About