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Development of a new Dietary Regimen for Mice, Which Suppresses Spontaneous Tumors

开发一种新的小鼠饮食方案，可抑制自发性肿瘤

基本信息

批准号：
01870027
负责人：
KAMIYAMA Sigetosi
金额：
$ 4.93万
依托单位：
Akita University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

Chronic bioassays are one of obligatory requlrement to register chemicals or drugs for human or veterinary uses. Common protocols use rats. and mice for choice of animals for chronic bioassays because of the con'ven3. ence and the abundance of historical data.It is well known that mice have very high incidence of tumors specific to strains. In general, the susceptibility of inbred strains and their hybrids to specific tumor induction by rodent carcinogens is related to the frequencies of spontaneous tumors of the same type.Energy restriction (ER) retards aging processes and extends life-span of rodents. The major causes of natural causes of mortalities of rodents are neoplasms. Inhibition of tumor growth by ER appears to play a primary role in expanding longevities of rodents.In the present study, we investigated the effects of ER on the sponteneously occuring mammary tumors in SHN mice and on dose-response relationship between asbestos and pulmonary adenocarcinoma in A/J mice.ER sppressed mouse mamary tumors in SHN mice completely while about 65% of the control mice had developed mammary tumors by 28 months of age. Energy restriction was shown to suppress mouse mammary tumor virus (MMTV) gene expression. Altogether, ER was concluded to inhibit mammary tumor development by decreasing gene expression of MMTV, by keeping the mammary glands immature, and by suppression of prolactin production.The increases in dose levels of asbestos results in the increases in both tumor sizes and numbers of tumori3 in ER mice. In agreement with the above trend, the ratio of tumor free mice decreased in a dose-associated manner. In contrast, an apparent dose-associated increases of tumor sizes or number of tumors were not found in control diet groups.The present study demonstrated that genetic backgrounds may perturbs the chronic bioassay. The energy restriction, however, can provide a very powerful tool to produce noise-free chronic bioassays.

慢性生物测定是注册人用或兽用化学品或药物的强制性要求之一。常见的方案使用老鼠。和小鼠用于慢性生物测定的动物选择，因为conven 3。事实和丰富的历史数据。众所周知，小鼠具有非常高的肿瘤发生率，特异于菌株。一般来说，近交系及其杂交种对致癌物诱发肿瘤的敏感性与同类动物自发性肿瘤的发生率有关，能量限制（Energy restriction，ER）可延缓衰老过程，延长寿命。啮齿类动物自然死亡的主要原因是肿瘤。ER抑制肿瘤生长似乎在延长啮齿动物寿命方面起主要作用。在本研究中，本实验观察了雌激素受体（ER）对SHN小鼠自发性乳腺肿瘤的影响，以及对石棉肺腺癌的剂量-反应关系的影响，结果表明，ER对SHN小鼠自发性乳腺肿瘤有完全的抑制作用，而对石棉肺腺癌有65%的抑制作用。的对照组小鼠在28个月大时发生了乳腺肿瘤。能量限制抑制小鼠乳腺肿瘤病毒（MMTV）基因的表达。总之，ER通过降低MMTV的基因表达、保持乳腺不成熟和抑制催乳素的产生来抑制乳腺肿瘤的发展。石棉剂量水平的增加导致ER小鼠中肿瘤大小和肿瘤数量的增加3。与上述趋势一致，无肿瘤小鼠的比例以剂量相关的方式降低。与此相反，在对照饮食组中没有发现明显的剂量相关的肿瘤大小或肿瘤数量的增加。本研究表明遗传背景可能会干扰慢性生物测定。然而，能量限制可以提供一个非常强大的工具来产生无噪声的慢性生物测定。