Suppressive effect of liver tumor-promoting activities in rats subjected to combined administration of phenobarbital and piperonyl butoxide.
Suppressive effect of liver tumor-promoting activities in rats subjected to combined administration of phenobarbital and piperonyl butoxide.
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苯巴比妥和胡椒基丁醚联合给药对大鼠肝脏肿瘤促进活性的抑制作用。
DOI：
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发表时间：
2013
影响因子：
2
通讯作者：
K. Mitsumori
中科院分区：
文献类型：
--
作者：
R. Morita;A. Yafune;A. Shiraki;Megu Itahashi;Hirotoshi Akane;F. Nakane;Kazuhiko Suzuki;M. Shibutani;K. Mitsumori
苯巴比妥（PB）是细胞色素P450（CYP）2B诱导剂，胡椒基丁醚（PBO）是CYP 1A/2B诱导剂。这些诱导剂对大鼠具有肝脏肿瘤促进作用。在这项研究中，我们进行了大鼠两阶段肝癌生物测定，以检查PB和PBO联合给药的促肿瘤作用。雄性大鼠接受腹腔注射N-二乙基亚硝胺（DEN）的启动。DEN给药后两周，大鼠被给予PB（60或120 ppm的饮用水），PBO（1，250或2，500 ppm的饮食）或60 ppm PB+1，250 ppm PBO 6周。PB/PBO治疗后一周，所有大鼠均接受三分之二部分肝切除术。为了评估联合给药的效果，我们使用了两个统计相加模型。在等加性模型中，PB+PBO组GST-P阳性灶面积平均值显著低于高PB组和高PBO组。在异加性模型中，PB+PBO组的Cyp 1a 1 mRNA水平和微粒体活性氧（ROS）产生的净值显著低于低PB组和低PBO组。而PB+PBO组PCNA阳性肝细胞比例、Cyp 2b 1/2、Gstm 3、Gpx 2和Nqo 1的mRNA水平以及硫代巴比妥酸反应物水平无交互作用。这些结果表明，PB和PBO联合给药对大鼠肝脏促肿瘤活性产生抑制作用，这是由于抑制CYP 1A诱导而抑制微粒体ROS产生所致。
Phenobarbital (PB) is a cytochrome P450 (CYP) 2B inducer, and piperonyl butoxide (PBO) is a CYP1A/2B inducer. These inducers have liver tumor-promoting effects in rats. In this study, we performed a rat two-stage liver carcinogenesis bioassay to examine the tumor-promoting effect of PB and PBO co-administration. Male rats received an intraperitoneal injection of N-diethylnitrosamine (DEN) for initiation. Two weeks after DEN administration, rats were given PB (60 or 120 ppm in drinking water), PBO (1,250 or 2,500 ppm in diet) or 60 ppm PB+1,250 ppm PBO for 6 weeks. One week after the PB/PBO treatment, all rats were subjected to a two-thirds partial hepatectomy. To evaluate the effect of the combined administration, we used two statistical additive models. In the isoadditive model, the average values of the area of GST-P positive foci in the PB+PBO group were significantly lower than those in the High PB or High PBO groups. In the heteroadditive model, the net values of Cyp1a1 mRNA level and microsomal reactive oxygen species (ROS) production in the PB+PBO group were significantly lower than the sum of those in the Low PB or Low PBO groups. On the contrary, there was no interactive effect in the PCNA-positive hepatocyte ratio, mRNA levels of Cyp2b1/2, Gstm3, Gpx2 and Nqo1, and the level of thiobarbituric acid-reactive substances in the PB+PBO group. These results suggest that PB and PBO co-administration causes suppressive effects in liver tumor-promoting activity in rats resulting from inhibited microsomal ROS production because of suppression of CYP1A induction.
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影响因子：
7.4
作者：
Puntarulo, S;Cederbaum, AI
通讯作者：
Cederbaum, AI
影响因子：
3.8
作者：
S. C. Serron;N. Dwivedi;W. Backes
通讯作者：
S. C. Serron;N. Dwivedi;W. Backes
影响因子：
3.8
作者：
Reisman, Scott A.;Yeager, Ronnie L.;Klaassen, Curtis D.
通讯作者：
Klaassen, Curtis D.
DOI：
10.1073/pnas.81.6.1696
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHESIS, PL;LEVIN, DE;AMES, BN
通讯作者：
AMES, BN