BIOLOGY OF THE MOUSE HEPATOCARCINOGENESIS

本研究的目的是检验这一假设， 肥胖阶段，无论其原因，提供了刺激， 增加显微镜下肝细胞肿瘤的生长速度， 老鼠. 临床意义是， 对于肿瘤生长刺激， 那些在肿瘤发生前就变得肥胖的人。 立体- 该实验室开发的基于计算机的方法将用于 精确测定大量微观生物的生长速率， 通过单次注射二乙基亚硝胺引发的肿瘤， 15日龄小鼠 这项研究将采用3种不同的肥胖模型 诱导（卵巢切除术，腹内侧下丘脑立体定向损伤， 和高可口的饮食喂养），这在宿主的效率不同 能源使用。 肿瘤生长的动力学将与肿瘤的生长相关。 体重增加率和身体成分（脂肪和蛋白质）的变化 在肥胖发展的动态和稳定阶段， 模型 由于下丘脑损伤不会发生真正的生长， 模型，它的研究可以帮助区分胴体脂肪的影响， 蛋白质沉积 卵巢激素下降的直接作用， 刺激肿瘤生长将通过将卵巢植入 致癌物处理的卵巢肥大小鼠的脾脏--一种维持脾脏功能的程序 门静脉血激素水平升高，同时降低全身水平。 更有可能的间接影响，也将进行测试， 抑制卵巢过度分泌小鼠的食物摄入和体重增加。 脂肪细胞数量、大小和脂蛋白脂酶变化的作用 含量、血清胰岛素和葡萄糖以及胰岛素和EGF受体 也将研究肥胖刺激的可能影响， 卵巢切除和下丘脑损伤的影响。

The objective of this study is to test the hypothesis that the dynamic phase of obesity, regardless of its cause, provides a stimulus to increase the growth rate of microscopic hepatocellular neoplasms in the mouse. The clinical implication is that patients who becomes obese after tumor initiation are at much greater risk for tumor growth stimulation that those who becomes obese prior to tumor initiation. Stereologic- computer based methods developed in this laboratory will be used to accurately determine the growth rates of large numbers of microscopic tumors that were initiated by single injections of diethylnitrosamine in 15 day old mice. The study will employ 3 different models of obesity induction (ovariectomy, ventromedial hypothalamic stereotactic injury, and feeding of highly palatable diet) which vary in the host's efficiency of energy use. The kinetics of tumor growth will be correlated with the rate of weight gain, and change in body composition (fat and protein) during the dynamic and stable phases of obesity development in the 3 models. Since true growth does not occur in the hypothalamic injury model, its study can help to distinguish the effects of carcass fat from protein deposition. A direct role of a decline in ovarian hormones in stimulating tumor growth will be studied by implanting ovaries into the spleens of carcinogen treated ovexed mice- a procedure which maintains a high level of portal blood hormones while reducing the systemic level. The more likely indirect effect of ovex will also be tested by constraining the food intake and weight gain of mice that are ovexed. The roles of changes in adipocyte number, size and lipoprotein lipase content, serum insulin and glucose, and receptors for insulin and EGF will also be studied as possible effects of the obesity stimulating effect of ovariectomy and hypothalamic injury.