Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea:: primary role of caffeine
Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea:: primary role of caffeine
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DOI：
10.1093/carcin/bgm237
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发表时间：
2008-08-01
期刊：
影响因子：
4.7
通讯作者：
Williams, David E.
中科院分区：
文献类型：
--
作者：
Castro, David J.;Yu, Zhen;Williams, David E.
我们的实验室最近开发了一种通过多环芳烃二苯并[a,l]芘（DBP）经胎盘诱导淋巴瘤、肺癌和肝癌的小鼠模型。与 129S1/SvIm 雄性交配的怀孕 B6129SF1 雌性在妊娠第 17 天接受口服剂量 15 mg/kg DBP 治疗。从妊娠第 0 天开始，给母鼠喂食（随意）缓冲水、0.5% 绿茶、0.5% 脱咖啡因绿茶、咖啡因或表没食子儿茶素-3-没食子酸酯 (EGCG)（两者的浓度与茶中的浓度相同）。茶（以及相应的咖啡因和 EGCG）的浓度在进入妊娠中期时增加至 1.0%，在妊娠晚期开始时增加至 1.5%，并继续保持在 1.5%，直到幼犬在 21 日龄断奶。后代用正常饮用水和AIN93G饮食饲养。正如我们之前的研究中所见，从 2 个月大开始，后代因侵袭性 T 细胞淋巴瘤而出现显着死亡。摄入含咖啡因的绿茶（而非不含咖啡因的绿茶）对降低死亡率具有适度但显着的保护作用（P = 0.03）。咖啡因提供了更强大的保护（P = 0.006），但 EGCG 没有效果。后代也出现了 DBP 依赖性肺腺瘤。相对于对照组，所有治疗均显着降低了肺肿瘤的多样性（P < 0.02）。与对照组相比，EGCG 在减少肿瘤负荷方面最有效（P = 0.005），平均减少 40% 以上。作为化学预防机制，母体肝脏中细胞色素 P450 (Cyp)1b1 的诱导可能会降低胎儿 DBP 的生物利用度。这是首次证明母亲在怀孕和哺乳期间摄入绿茶可以预防经胎盘致癌。
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.