Quantitative subcellular distribution of platinum in rat tissues following i.v. bolus and i.v. infusion of cisplatin.
An analysis of the subcellular localization of platinum was conducted in Sprague-Dawley (SD) rats following administration of an i.v. dose of 6 mg/kg cisplatin (bolus and infusion). Biodistribution studies were carried out in the liver and kidney of control animals, as well as in these same organs and in the tumor (Walker 256 adenocarcinoma) of SD rats. The results obtained illustrate that in addition to the platination of DNA in these tissues, significant amounts of Pt are also incorporated into the chromosomal protein (CP) and cytosolic fractions. The localization of Pt in the cytosolic fractions was highest in the kidney, followed by the tumor, and lowest in the liver when determined as the fractional percentage of the total amount of injected drug (%ID/g). The significance of such cytosolic and CP localization of Pt is not known at this time, but they may be involved in the cytotoxic effects of cisplatin, as this drug is cytotoxic to tumors and kidneys but not to the liver. The localization of cisplatin in the subcellular fractions of liver, kidney, and tumor showed a trend toward being higher after i.v. infusion than after i.v. bolus administration of the drug.
Parti
R
R
Radiopharmacy Program, University of Southern California, Los Angeles 90033.
Wolf
W
W
D000818:Animals; D002279:Carcinoma 256, Walker / Q000188:drug therapy / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009368:Neoplasm Transplantation; D010984:Platinum / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D002868:Chromosomal Proteins, Non-Histone; D004273:DNA, Neoplasm; D010984:Platinum; D002945:Cisplatin