https://scholars.lib.ntu.edu.tw/handle/123456789/639358
標題: | Dose-response formation of N7-(3-benzo[1,3]dioxol-5-yl-2-hydroxypropyl)guanine in liver and urine correlates with micronucleated reticulocyte frequencies in mice administered safrole oxide | 作者: | KUEN-YUH WU Wei, Yu-Tzu YU-SYUAN LUO Shen, Li-Chin Chang, Bao-Suei Chen, Ya-Yin Huang, Yan-Chi Huang, Hui-Fen Chung, Wen-Sheng Chiang, Su-Yin |
關鍵字: | Isotope dilution; Liquid chromatography-tandem mass spectrometry; Micronuclei; N7-guanine adduct; Safrole; Safrole oxide | 公開日期: | 十一月-2023 | 出版社: | Elsevier Science Ltd | 卷: | 181 | 來源出版物: | Food And Chemical Toxicology | 摘要: | Safrole oxide (SAFO), a metabolite of naturally occurring hepatocarcinogen safrole, is implicated in causing DNA adduct formation. Our previous study first detected the most abundant SAFO-induced DNA adduct, N7-(3-benzo[1,3] dioxol-5-yl-2-hydroxypropyl)guanine (N7γ-SAFO-G), in mouse urine using a well-developed isotope-dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (ID-HPLC-ESI-MS/MS) method. This study further elucidated the genotoxic mode of action of SAFO in mice treated with SAFO 30, 60, 90, or 120 mg/kg for 28 days. The ID-HPLC-ESI-MS/MS method detected N7γ-SAFO-G with excellent sensitivity and specificity in mouse liver and urine of SAFO-treated mice. Our data provide the first direct evidence of SAFO-DNA adduct formation in rodent tissues. N7γ-SAFO-G levels in liver were significantly increased by SAFO 120 mg/kg compared with SAFO 30 mg/kg, suggesting rapid spontaneous or enzymatic depurination of N7γ-SAFO-G in tissue DNA. Urinary N7γ-SAFO-G exhibited a sublinear dose response. Moreover, the micronucleated peripheral reticulocyte frequencies increased dose-dependently and significantly correlated with N7γ-SAFO-G levels in liver (r = 0.8647; p < 0.0001) and urine (r = 0.846; p < 0.0001). Our study suggests that safrole-mediated genotoxicity may be caused partly by its metabolic activation to SAFO and that urinary N7γ-SAFO-G may serve as a chemically-specific cancer risk biomarker for safrole exposure. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/639358 | ISSN: | 02786915 | DOI: | 10.1016/j.fct.2023.114056 |
顯示於: | 食品安全與健康研究所 |
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