Castro David J, Yu Zhen, Löhr Christiane V, Pereira Clifford B, Giovanini Jack N, Fischer Kay A, Orner Gayle A, Dashwood Roderick H, Williams David E
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.
Carcinogenesis. 2008 Aug;29(8):1581-6. doi: 10.1093/carcin/bgm237. Epub 2008 Jul 16.
Our laboratory recently developed a mouse model of transplacental induction of lymphoma, lung and liver cancer by the polycyclic aromatic hydrocarbon, dibenzo[a,l]pyrene (DBP). Pregnant B6129SF1 females, bred to 129S1/SvIm males, were treated on day 17 of gestation with an oral dose of 15 mg/kg DBP. Beginning on day 0 of gestation, dams were given (ad lib) buffered water, 0.5% green tea, 0.5% decaffeinated green tea, caffeine or epigallocatechin-3-gallate (EGCG) (both at equivalent concentrations found in tea). The concentration of the teas (and corresponding caffeine and EGCG) was increased to 1.0% upon entering the second trimester, 1.5% at onset of the third trimester and continued at 1.5% until pups were weaned at 21 days of age. Offspring were raised with normal drinking water and AIN93G diet. Beginning at 2 months of age, offspring experienced significant mortalities due to an aggressive T-cell lymphoma as seen in our previous studies. Ingestion of caffeinated, but not decaffeinated, green tea provided modest but significant protection (P = 0.03) against mortality. Caffeine provided a more robust (P = 0.006) protection, but EGCG was without effect. Offspring also developed DBP-dependent lung adenomas. All treatments significantly reduced lung tumor multiplicity relative to controls (P < 0.02). EGCG was most effective at decreasing tumor burden (P = 0.005) by on average over 40% compared with controls. Induction of Cytochrome P450 (Cyp)1b1 in maternal liver may reduce bioavailability of DBP to the fetus as a mechanism of chemoprevention. This is the first demonstration that maternal ingestion of green tea, during pregnancy and nursing, provides protection against transplacental carcinogenesis.
我们实验室最近开发了一种小鼠模型，用于研究多环芳烃二苯并[a,l]芘（DBP）经胎盘诱导淋巴瘤、肺癌和肝癌的情况。将怀孕的B6129SF1雌性小鼠与129S1/SvIm雄性小鼠交配，在妊娠第17天给母鼠口服15 mg/kg的DBP。从妊娠第0天开始，给母鼠自由饮用缓冲水、0.5%的绿茶、0.5%的脱咖啡因绿茶、咖啡因或表没食子儿茶素-3-没食子酸酯（EGCG）（浓度均与茶中所含相当）。进入妊娠中期后，茶（以及相应的咖啡因和EGCG）的浓度增至1.0%，妊娠晚期开始时增至1.5%，并持续保持在1.5%，直至幼崽在21日龄断奶。后代用正常饮用水和AIN93G饲料饲养。从2月龄开始，如我们之前的研究所示，后代因侵袭性T细胞淋巴瘤出现了显著的死亡情况。摄入含咖啡因而非脱咖啡因的绿茶对死亡率有适度但显著的保护作用（P = 0.03）。咖啡因提供了更强的保护作用（P = 0.006），但EGCG没有效果。后代还出现了依赖DBP的肺腺瘤。与对照组相比，所有处理均显著降低了肺肿瘤的多发性（P < 0.02）。EGCG在降低肿瘤负担方面最有效（P = 0.005），与对照组相比平均降低超过40%。母鼠肝脏中细胞色素P450（Cyp）1b1的诱导可能会降低DBP对胎儿的生物利用度，这是一种化学预防机制。这是首次证明母鼠在怀孕和哺乳期间摄入绿茶可预防经胎盘致癌作用。
