Effect of bismuth nitrate given in combination withcis-diamminedichloroplatinum(II) on the antitumor activity and renal toxicity of the latter in nude mice inoculated with human bladder tumor

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The effects of bismuth nitrate pretreatment on the toxicity and antitumor activity of cis-diamminedichloroplatinum (cisplatin, CDDP) were examined in nude mice that had been inoculated with human bladder-tumor tissue. Pretreatment with bismuth nitrate depressed the renal toxicity of CDDP without compromising its activity against a transplantable human bladder tumor. Renal metallothionein (MT) and bismuth (Bi) levels in nude mice were markedly increased by Bi preadministration, but no significant MT induction was observed in inoculated human bladder-tumor tissue in which only a trace amount of Bi was incorporated. Furthermore, it was confirmed that tumor platinum (Pt) concentrations in CDDP-treated mice were not affected by Bi pretreatment. Thus, the administration of Bi compounds prior to chemotherapy with CDDP may provide an effective mode of treatment for advanced bladder tumors.

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