1987 Fiscal Year Final Research Report Summary
Relationship of hepatocarcinogenesis and form of cytochrome P-450 highly active to aflatoxin B_1.
| Project/Area Number |
61571103
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | 国立衛生試験所 |
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Principal Investigator |
TAKANAKA Akira 国立衛生試験所, 安全性生物試験研究センター・薬理部, 部長 (60079308)
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| Co-Investigator(Kenkyū-buntansha) |
簾内 桃子 国立衛生試験所, 安全性生物試験研究センター・薬理部, 研究員
福原 守雄 国立公衆衛生院, 衛生薬学部, 室長 (40083745)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Cytochrome P-450 / hamster / アフラトキシンB_1 |
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| Research Abstract |
S9 mixture of PCB-treated hamsters was shown to be highly active in the induction of the mutagenicity of aflatoxin B_1 in Ames test on Salmonella typhimurium TA100. This activity of the hamster is more then 20 times higher than that of PCB-treated rats and other experimental animals. The activity was more induced by the threatment of hamsters with 3-methylcholanthrene than with phenobarbital and was present in the hepatic microsomes. The isolation of cytochrome P-450s from hepatic microsomes of 3-methylcholanthrene-treated hamsters demonstrated the existence of 3 forms of cytochrome P-450, consisting og two major forms(Form I and Form II) and one minor form(Form III). These forms were different each other in their physicochemical and catalytic properties. Of these,Form I,having its absorption maximum at 448.5 in its Co-complex of reduced form,low spin ferric ion and a molecular weight of 5,600,was shown to be highly active in the induction of aflatoxin B_1 mutagenicity, Form I could specifically activate other aflatoxin B_1-related mycotoxins such as sterigmatocystin and 0-methylsterigmatocystin. By Western blot,using the antibodies to the major forms of cytochrome P-450s from hamsters, Form I was shown not to exist in the hepatic microsomes of other experimentasl animals treated with 3-methylcholanthrene, While Form II was shown to exist in hepatic pmicrosomes of almost all the animals studied.
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