| Project/Area Number |
05671326
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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 |
Urology
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| Research Institution | OITA MEDICAL UNIVERSITY |
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Principal Investigator |
NAKAGAWA Masayuki Oita Medical University, Department of Urology, Assistant Professor, 医学部, 講師 (90164144)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | cisplatinum / drug resistance / prostatic cancer / 細胞内CDDP蓄積量 / DNA修復能 / シスプラチン / 耐性 / 細胞内蓄積 / グルタチオン / DNA修複 |
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| Research Abstract |
We have isolated cisplatinum (CDDP) -resistant cell lines, P/CDP4 and P/CDP5, from human PC-3 prostatic cancer cells after a stepwise exposure to CDDP to elucidate mechanisms of cisplatinum-resistance in urinary tumors.P/CDP4 and P/CDP5 showed 11-fold and 23-fold higher resistance to CDDP than did PC-3.P/CDP5 was cross-resistant to carboplatin, mitomycin C,etoposide, m-AMSA,bleomycin and UV irradiation.Alkaline elution of DNA showed an increased amount of DNA interstrand cross-links in PC-3 but not in P/CDP5 when PC-3 and P/CDP5 were cultured with CDDP.Flameless atomic absorption spectrophotometry revealed that intracellular accumulation of CDDP in P/CDP4 and P/CDP5 was decreased to 18% to 34% and 9% to 18% of that PC-3, respectively, when PC-3 and its CDDP-resistant counterparts were incubated with 5 and 10 mug/ml of CDDP for 24 hrs.These data suggest that decreased drug accumulation is involved in the development of CDDP-resistance in the PC-3 cell line.
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