| Project/Area Number |
01870027
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Hygiene
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| Research Institution | Akita University School of Medicine |
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Principal Investigator |
KAMIYAMA Sigetosi Akita University School of Medicine Department of Hygiene, Professor, 医学部, 教授 (80004547)
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| Co-Investigator(Kenkyū-buntansha) |
KOIZUMI Akio Akita Univ. Schl of Med. Assoc. Prof., 医学部, 助教授 (50124574)
TAKAHASI Hirosi National Institute for Environ. Sciences Group Leader, 動物施設, 室長 (80101046)
HIRANO Seisiro National Institute for Environ. Sciences Researcher, 環境保健部, 主任研究員 (20150162)
SUZUKI Kazuo National Institute for Environ. Sciences Group Leader, 環境保健部, 室長 (90109918)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1989: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | Mouse / Energy Restriction / Mammary Tumor / Mouse Mammary Tumor Virus / Asbestos / Pulmonary Adenoma / Dose-Response Relationship / A / Jマウス / エネルギ-制限 / 用量-反応関係 / 制限食 / カロリ- / 自然発癌 / 肺癌 |
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| Research Abstract |
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.
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