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Inhibition of mutagenicity of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by aqueous extract (crude) and organic extract (pulegone) of Calamintha nepeta. Calamintha nepeta (CN) is an aromatic mint used as a traditional medicinal herb in Europe and the Mediterranean for its broad range of biological activities; these include anti-inflammatory, antioxidant, antimicrobial, anti-ulcer, insecticidal, and cancer-preventive properties. Previous studies have revealed the apoptotic and cancer-preventing attributes of its major organic fractions: pulegone (PUL, 2760 ppm), D-limonene (385 ppm), and menthone (590 ppm). PUL (6.4 - 800 mg/plate) was not mutagenic in Salmonella typhimurium TA97, TA98, TA100, TA1535, or TA1537 regardless of S9 metabolic activation. When cooking at high temperatures, creatine, sugars, and amino acids begin to produce 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which yielded positive results in the Ames mutagenicity tests. PhIP is one of the most abundant heterocyclic amines (HCAs) in cooked meat and the U.S. Department of Health and Human Services’ National Toxicology Program has denounced it as "reasonably anticipated to be a human carcinogen". Thus, cancer of the prostate, breast, lung, esophagus, stomach, and colorectal may be related to high intake and high exposure to PhIP. This study assessed and compared the effects of total aqueous and organic extracts of CN on PhIP-induced mutagenesis using TA98 as the bacterial tester strain and rat liver 9000 x g supernatant (S9) as the metabolic activation system. Our results showed that both the crude aqueous extract and organic essential oil extract (PUL) of the herb significantly inhibited the mutagenicity of PhIP (both 0.1 and 1 µg/plate), bioactivated by S9 (800 mg/plate), in a dose-response fashion (p < 0.05). The percent inhibition of revertant formation for these two extracts against 0.1 µg/plate of PhIP were: 32%, 74%, 79%, 84%, and 90% regarding the total aqueous extract (0.1, 0.5, 1.0, 1.5, and 3 mg/plate) and 28%, 36%, 64%, 75%, and 97% for the PUL essential oil of the organic extract (1.0, 10, 50, 100, and 200 µg/plate). Both the aqueous and organic extracts revealed the same trend of significance (p < 0.05) concerning percent inhibition of revertant formation against PhIP (1 µg/plate) in a dose-response fashion. The organic fraction (PUL) maintained a stronger antimutagenic effect in comparison to the total aqueous effect. These results suggest that both aqueous crude extract and organic PUL extract of CN contain antimutagenic phytochemicals concerning PhIP-induced mutagenicity. Further study of their modulatory effects on metabolism and the DNA binding of PhIP is warranted to reveal the potential antimutagenicity mechanism and their chemopreventive properties against PhIP and potentially against other HCAs. Citation Format: Yanlingxue Wan, Ryan Hayes, Joshua Li, Kristin Ferrer, Padma T. Uppula, Brian Yuen Yau Wong. Inhibition of mutagenicity of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP) by aqueous extract (crude) and organic extract (pulegone) of Calamintha nepeta. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5091.
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