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Antimutagenic effects of polyphenolic compounds
1Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, CA 92350.
Abstract:
Smokers expose themselves to potent carcinogens daily. One of them is the nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Since estimates are that humans consume 1 g of phenolic compounds/day, we investigated the inhibitory effects of five structurally related polyphenolic compounds on the mutagenicity of NNK in Salmonella typhimurium TA1535. NNK at a concentration of 80 mM was activated by hamster liver microsomes. The antimutagenic efficacies were dose-related between the non-toxic concentrations of 0.1 and 0.5 mmol/dish in the following order: esculetin > ellagic acid > (+)-catechin > propyl gallate > (-)esculin. At the highest non-toxic dose tested (0.5 mmol/dish), these polyphenolics inhibited mutagenesis in TA1535 by 77%, 67%, 62%, 59% and 53%, respectively. The results of this study demonstrated that polyphenolic compounds may inhibit the activation of NNK.
Insights
Polyphenolic compounds can inhibit the mutagenicity of NNK, a potent carcinogen found in tobacco smoke. Esculetin showed the strongest effect, reducing NNK-induced mutations by 77%.
Area of Science:
- Biochemistry
- Toxicology
- Nutraceuticals
Background:
- Smokers are exposed to potent carcinogens like NNK.
- Phenolic compounds are consumed daily by humans.
- NNK is a nicotine-derived nitrosamine and a known mutagen.
Purpose of the Study:
- To investigate the inhibitory effects of five polyphenolic compounds on NNK mutagenicity.
- To determine the dose-response relationship of these compounds.
- To compare the antimutagenic efficacies of esculetin, ellagic acid, (+)-catechin, propyl gallate, and (-)-esculin.
Main Methods:
- Using Salmonella typhimurium TA1535 as a bacterial mutagenicity test system.
- Activating NNK (80 mM) with hamster liver microsomes.
- Testing non-toxic concentrations of polyphenols (0.1–0.5 mmol/dish).
Main Results:
- Antimutagenic efficacies were dose-related.
- Esculetin (77%), ellagic acid (67%), (+)-catechin (62%), propyl gallate (59%), and (-)-esculin (53%) inhibited NNK-induced mutagenesis at 0.5 mmol/dish.
- The order of efficacy was esculetin > ellagic acid > (+)-catechin > propyl gallate > (-)-esculin.
Conclusions:
- Polyphenolic compounds demonstrate significant antimutagenic activity against NNK.
- These findings suggest a potential role for dietary polyphenols in mitigating NNK-induced genotoxicity.
- Further research into the mechanisms of NNK inhibition by polyphenols is warranted.