| Project/Area Number |
03670634
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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 |
Digestive surgery
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| Research Institution | Saga Medical School |
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Principal Investigator |
MIYAZAKI Kohji Saga Medical School, Surgery, Assistant Professor, 医学部, 講師 (30159173)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Liver cirrhosis / Chemical carcinogenesis / DNA injury / Reduced glutathione / Cytochrome P-450 / Alkaline elution / チトクロ-ムPー450 |
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| Research Abstract |
The effects of reduced glutathione (GSH) and ethanol on aflatoxin B_1 AFB_1)-induced DNA single strand breaks and AFB_1-DNA adduct formation were studied in primary cultured hepatocytes. Buthionine sulphoximine (BSO) decreased intracellular GSH to 13% of those of control levels, increased DNA fragmentation of AFB_1-treated hepatocytes by over 17% of those without BSO. Thus a decrease in hepatocyte GSH levels increased AFB_1-induced DNA damage. Although ethanol in itself did not induce DNA damage, a combination of BSO and ethanol increased the percentage by over 23% of that with BSO only. BSO significantly enhanced the formation of [^3H]AFB_1-DNA adducts and ethanol further increased it in the presence of BSO, whereas ethanol did not affect the amount of GSH, total cytochrome P-450, glutathione S-transferase and epoxide hydrolase in cultured hepatocytes. However, GSH-depleted rat hepatocytes exposed to ethanol significantly increased the level of cytochrome P450IIIA, which activates AFB_1. The enhancing effects of ethanol in the presence of BSO are probably due to the induction of this enzyme in rat hepatocytes.
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