| Project/Area Number |
62480145
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | 国立衛生試験所 |
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Principal Investigator |
HAYASHI Yuzo National Institute of Hygienic Sciences.Division of Pathology, Division Head., 病理部, 部長 (40142129)
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| Co-Investigator(Kenkyū-buntansha) |
MAEKAWA Akihiko National Institute of Hygienic Sciences.Division of Pathology, Section Head., 病理部, 室長 (30106182)
IMAIDA Katsumi National Institute of Hygienic Sciences.Division of Pathology, Section Head., 病理部, 室長 (90160043)
TAKAHASHI Michihito National Institute of Hygienic Sciences.Division of Pathology, Section Head., 病理部, 室長 (30080005)
黒川 雄二 国立衛生試験所, 毒性部, 部長 (50006102)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1989: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | 4-Hydroxyaminoquinoline 1-oxide (HAQO) / Age-related alterations of adrenal cortex / Age-related alterations of pancreas / Age-related alterations of peripheral nerves / ACTH / Cholecystokinin / 4ーhydroxyaminoquinolinel-oxide / 副腎皮質腫瘍 / peliosis adrenalis / 4-hvdroxyaminoquinoline 1-oxide / 大豆トリプシン阻害物質(SBT1) / basophilic acihar foci / 4ーHydroxyaminoguinoline 1ーoxide / Peliosis adrenalis / Adriamycin / 加齢性腎症 / 糸球体上皮細胞 |
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| Research Abstract |
Based on genetic concepts of aging mechanism, it is assumed that chemicals with potentials of causing DNA damage can elicit age- associated alterations in their target sites. The present studies were attempted, aiming at ascertainment of this possibility, to examine whether administration of 4-hydroxyaminoquinoline 1-oxide (HAQO), a potent genotoxic,carcinogen to rats can induce age-related alterations in the target organs.
8 weekly i.v. injections of HAQO at a dose of 5 mg/kg to rats resulted in ataxia and sensory disturbances of hindlimbs. Histopathological examination revealed the occurrence of axonal degeneration in the spinal cord and brain.preferentially affecting the posterior funiculus and trigeminal nerve. Nerve cell bodies of the dorsal spinal ganglia and the trigeminal ganglia were shown to have various grades of degenerative changes such as cytoplasmic vacuolation, accumulation of lipofuscin granules. focal depletion of ribosomes, irregular contour of nuclear envelope and disarrangement of neurofilament bundles. A single i.v. injection of HAQO at a dose of 7 mg/kg was shown to cause peliosis adrenalis in the adrenal of female rats and atypical acinar cell foci, so-called basophilic foci, in the exocrine pancreas of male rats. These lesions are known to occur in aged rats. Additional experiments cystokinin could inhibit the occurrence of either HAQO-induced peliosis adrenalis or pancreatic basophilic foci.
These findings suggest a possibility that (1) DNA-damaging agents can promote the occurrence of age-related organ lesions and (2) growth/trophic factors can inhibit the development of such lesions.
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