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Modification of in vivo heterocyclic amine genotoxicity by dietary flavonoids
A J Alldrick1, B G Lake, I R Rowland
1British Industrial Biological Research Association, Carshalton, Surrey, UK.
Abstract:
Female BALB/c mice were fed diets containing equimolar amounts of quercetin or its glycoside, rutin, for 5 weeks. These mice were used either in host-mediated bacterial mutation assays or as sources of hepatic microsomes. In host-mediated bacterial mutation assays using radiolabelled mutagens, the heterocyclic amines 2-amino-3,5-dimethyl[4,5-f]imidazoquinoline (MeIQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) induced greater numbers of revertants in mice fed either of the flavonoid diets compared with control. Experiments using hepatic microsomes revealed that although feeding mice either flavonoid produced slight changes in some parameters of hepatic xenobiotic metabolism (mixed function oxidase and glutathione transferase activities), microsomes from quercetin-fed mice were more potent activators of both MeIQ and Trp-P-2 compared with microsomes from control or rutin-fed mice. This difference in microsomal ability may be due to the different biological availability of the two flavonoids within the gastrointestinal tract.
Insights
Quercetin and rutin diets increased mutagenic heterocyclic amine activity in mice. Quercetin-fed mice showed higher activation of mutagens by liver microsomes, possibly due to bioavailability differences.
Area of Science:
- Biochemistry
- Toxicology
- Nutritional Science
Background:
- Flavonoids like quercetin and rutin are plant compounds with potential health benefits.
- Heterocyclic amines (HCAs) are mutagens formed during cooking, posing health risks.
Purpose of the Study:
- To investigate the impact of dietary quercetin and rutin on the mutagenicity of HCAs in mice.
- To examine the effect of these flavonoids on hepatic xenobiotic metabolism.
Main Methods:
- Female BALB/c mice were fed diets containing quercetin or rutin for 5 weeks.
- Host-mediated bacterial mutation assays were performed using radiolabeled HCAs (MeIQ and Trp-P-2).
- Hepatic microsomes were isolated to assess xenobiotic metabolism activities and mutagen activation.
Main Results:
- Mice fed quercetin or rutin showed increased revertants in bacterial mutation assays with MeIQ and Trp-P-2 compared to controls.
- Hepatic microsomes from quercetin-fed mice exhibited enhanced activation of MeIQ and Trp-P-2.
- Slight alterations in mixed function oxidase and glutathione transferase activities were observed in both flavonoid-fed groups.
Conclusions:
- Dietary quercetin and rutin can modulate the mutagenic potential of HCAs in vivo.
- Quercetin appears more effective than rutin in enhancing HCA activation by hepatic microsomes, potentially due to differences in gastrointestinal bioavailability.