Abstract 4017: Inhibition of mutagenicity of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine)by Chinese medicinal herbs Scutellaria barbata and Oldenlandia diffusa

Abstract

Abstract Scutellaria barbata (SB) and Oldenlandia diffusa (OD) have been used in traditional Chinese medicine for treating liver, lung and rectal tumors. Recent research revealed that these two herbs were included in most of the herbal cancer treatment formulas in Taiwan hospitals. We previously showed that SB and OD inhibited mutagenesis, DNA binding and metabolism of aflatoxin B1 (AFB1) and benzo(a)pyrene (BaP) bioactivated by Aroclor 1254-induced rat S9. PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is produced from high cooking temperature of creatine, sugars, and amino acids. It was demonstrated positive result in the Ames mutagenicity test. PhIP is one of the most abundant heterocyclic amines (HCAs) in cooked meat and has been announced as "reasonably anticipated to be a human carcinogen" by the U.S. Department of Health and Human Services National Toxicology Program. Cancer of the prostate, breast, lung, esophagus, stomach, and colorectum may be related to high intake and high exposure to PhIP. In this study, the effects of aqueous extracts of SB and OD on PhIP-induced mutagenesis using Salmonella typhimurium TA98 as the bacterial tester strain and rat liver 9000 x g supernatant (S9) as the metabolic activation system were assessed. Our results showed that SB and OD significantly inhibited the mutagenicity of PhIP (both 0.1 and 1µg/plate) bioactivated by S9 (800 mg/plate) in a dose-response fashion (p< 0.05). The percent inhibition of revertants formation of these two herbs against 0.1µg/plate of PhIP were 45%, 77%, and 87% for SB (1.5, 3, and 6 mg/plate) and 21%, 80%, and 95% for OD (1.5, 3, and 6 mg/plate), while the percent inhibition against 1 µg/plate of PhIP were similar to that of the 0.1 µg/plate (45%, 80%, 90% for SB and 44%, 81%, 93% for OD, respectively). There was a slight additive inhibition effect of the herbs in combination (SB + OD) at higher concentrations (60%, 85%, and 90%) against both concentrations of PhIP. These results suggested that OD and SB contain antimutagenic phytochemicals towards PhIP-induced mutagenicity. Further study of their modulation effects on metabolism and DNA binding of PhIP is warranted to reveal the potential anti-mutagenicity mechanism and their chemopreventive property against PhIP and potentially against other HCAs. Citation Format: Rayford Alva, Brian Yuen Yau Wong, John Tanner, Yanlingxue Wan, Padma Tadi Uppala, Ryan Hayes. Inhibition of mutagenicity of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine)by Chinese medicinal herbs Scutellaria barbata and Oldenlandia diffusa [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4017.