We have isolated cis-diamminedichloroplatinum (II) (CDDP)-resistant variants, P/CDP4 and P/CDP5, from human prostatic cancer PC-3 cells after a stepwise exposure to CDDP. 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 of PC-3, respectively, when PC-3 and its CDDP-resistant counterparts were incubated with 5 and 10 micrograms./ml. of CDDP for 24 hours. These data suggest that decreased drug accumulation is involved in the development of CDDP-resistance in the PC-3 cell line.
The ESSQ system showed moderate reliability for the video assessments by the referees. It was concluded that the video assessments by the referees were fair for all applicants, because the final qualification rates showed no significant differences among the referees.
To examine the sequential renal hemodynamic changes in experimental renovascular hypertension, the uninephrectomized dog was studied immediately after renal artery constriction, throughout chronic benign hypertension, and during malignant hypertension. Intrarenal resistance fell immediately after renal artery constriction, but rose above control within hours. Intrarenal infusion of teprotide resulted in vasodilatation during the first 3 days but failed to do so during the chronic phase of benign hypertension. During the transition from benign to malignant hypertension, angiotensin II-dependent renal vasoconstriction developed associated with natriuresis, plasma volume contraction and a vicious cycle of hyperreninemia and severe vascular damage.
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