Covalent binding of platinum to renal protein from sensitive and resistant guinea pigs treated with cisplatin: possible role in nephrotoxicity.
Covalent binding of platinum from the anticancer drug cisplatin has been determined in subcellular organelles from kidney and liver of guinea pig strains sensitive and resistant to the systemic toxicity of cisplatin. Organ distribution of platinum was similar between the two strains, but the sensitive animals (pigmented) excreted only half as much platinum in 24 hr as did the resistent animals (albino). Subcellular distribution of platinum in mitochondria, microsomes, and cytosol was approximately equal for both strains, but the sensitive animals had twice as much platinum bound covalently to cytosolic acid-insoluble protein as did the resistant animals. In the albino guinea pigs, concentrations of total platinum and of covalently bound platinum were greater in kidney subcellular organelles than in either liver or lung organelles, which may help explain the sensitivity of the kidney to the toxic effects of cisplatin.
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Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892.
Schweitzer
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D000818:Animals; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity*; D003600:Cytosol / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D010984:Platinum / Q000378:metabolism*; D011485:Protein Binding
D010984:Platinum; D002945:Cisplatin