Randerath K, van Golen K L, Dragan Y P, Pitot H C
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Carcinogenesis. 1992 Jan;13(1):125-30. doi: 10.1093/carcin/13.1.125.
The age-dependent effects of diet and of phenobarbital (PB), a known promoter of hepatocarcinogenesis, on indigenous DNA adducts (I-compounds) were studied by the 32P-post-labeling technique. Late-gestation female Sprague-Dawley rats were fed either AIN-76A semisynthetic or Teklad cereal-based diet. At 21 days after birth, the male pups were weaned and continued on the diets, with half of each dietary group receiving 0.05% PB mixed into the diet for 2, 4 and 8 months. Age-dependent increases in I-compound levels were observed. In addition, both the levels of individual I-compounds and the overall number of I-compounds were greater in rats fed the Teklad cereal-based diet than in those fed the AIN-76A diet. Independent of the parent diet, PB administration reduced the levels of the majority of I-compounds in a time-dependent manner. This effect of PB was detected earlier in the Teklad-fed than in the AIN-76A-fed group. In contrast to the I-compounds, a second group of spots, termed reverse I-compounds, declined between 2 and 4 months and, especially in AIN-76A-fed animals, tended to increase when PB was administered. It is hypothesized that alterations of DNA modification patterns may play a role in diet-modified hepatocarcinogenesis promoted by PB.
采用³²P后标记技术研究了饮食以及苯巴比妥（PB，一种已知的肝癌发生促进剂）对内源性DNA加合物（I-化合物）的年龄依赖性影响。妊娠后期的雌性斯普拉格-道利大鼠喂食AIN-76A半合成饲料或泰克莱德谷物基饲料。出生后21天，雄性幼崽断奶并继续喂食原饲料，每个饮食组中有一半接受混入0.05% PB的饲料，持续2、4和8个月。观察到I-化合物水平随年龄增加。此外，喂食泰克莱德谷物基饲料的大鼠中单个I-化合物的水平和I-化合物的总数均高于喂食AIN-76A饲料的大鼠。与基础饲料无关，PB给药以时间依赖性方式降低了大多数I-化合物的水平。在喂食泰克莱德饲料的组中比在喂食AIN-76A饲料的组中更早检测到PB的这种作用。与I-化合物相反，另一组斑点，称为反向I-化合物，在2至4个月之间减少，特别是在喂食AIN-76A饲料的动物中，当给予PB时往往会增加。据推测，DNA修饰模式的改变可能在PB促进的饮食修饰肝癌发生中起作用。
