In Vitro Cellular & Developmental Biology - Animal, 2015, 51(4):426-431.

Sex hormone modulation of both induction and inhibition of CYP1A by genistein in HepG2/C3A cells

Yitong Liu, Michael F. Santillo, Thomas J. Flynn, et al

Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied NutritionUS Food and Drug AdministrationLaurelUSA; Division of Public Health Informatics and Analytics, Office of Analytics and Outreach, Center for Food Safety and Applied NutritionUS Food and Drug AdministrationCollege ParkUSA

Genistein is a widely consumed phytoestrogen in dietary supplements and has been reported to play roles in both cancer prevention and promotion. These conflicting effects may be complicated by sex differences. Cytochrome P450 1A (CYP1A) participates in carcinogen activation and detoxification, and the enzyme may interact with genistein. Therefore, modulation of CYP1A by a combination of genistein and sex hormones could be responsible for sex differences related to cancer prevention and promotion. In the current study, a human liver cell line, HepG2/C3A, cultured in sex hormone-supplemented media was used to investigate the modulatory effect of genistein on CYP1A gene expression and activity. Genistein exerted both long-term (72 h) induction and short-term (immediate) inhibition of CYP1A activity in HepG2/C3A cells. In the long-term study, CYP1A gene expression and enzyme activity were induced to a greater extent in male hormone-supplemented cells than female ones. In the short-term study, CYP1A activity was inhibited more strongly by genistein in the male hormone-supplemented cells than in the female hormone-supplemented cells. These significant differences suggest that male hormones can modulate the effects of genistein on CYP1A gene expression and activity.

德国《体外细胞与发育生物-动物学》，2015

在 HepG2/C3A 细胞中由金雀异黄素诱导和抑制的 CYP1A的性激素调节
刘奕彤，米歇尔 F 山特鲁，汤玛斯 J 付丽妮，等
毒理学科，应用研究与安全评估办公室，食品安全和应用营养中心美国食品药物管理局LurellusA; 公共卫生信息和分析部门，分析和外联办公室，食品安全和应用营养中心美国食品和药物管理局学院公园美国

染料木黄酮是膳食补充剂中广泛使用的植物雌激素，据报道它们在癌症预防和促进中发挥作用。这些矛盾的影响可能由于性别差异而变得复杂。细胞色素P450 1A（CYP1A）参与致癌物激活和解毒，酶可与染料木素相互作用。因此，通过染料木素和性激素的组合调节CYP1A可能导致与癌症预防和促进相关的性别差异。在目前的研究中，使用人类肝细胞系HepG2 / C3A，在补充性激素的培养基中培养，研究染料木黄酮对CYP1A基因表达和活性的调节作用。染料木黄酮在HepG2 / C3A细胞中长期（72小时）诱导和短期（立即）抑制CYP1A活性。在长期研究中，CYP1A基因表达和酶活性在男性激素补充细胞中比雌性激素更大程度地诱导。在短期研究中，CYP1A活性在雌激素补充细胞中被染料木黄酮抑制得比雌激素补充细胞更强烈。这些显着差异表明，男性激素可以调节染料木黄酮对CYP1A基因表达和活性的影响。