Parti R, Wolf W
Radiopharmacy Program, University of Southern California, Los Angeles 90033.
Cancer Chemother Pharmacol. 1990;26(3):188-92. doi: 10.1007/BF02897197.
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.
在给Sprague-Dawley（SD）大鼠静脉注射6mg/kg顺铂（推注和输注）后，对铂的亚细胞定位进行了分析。在对照动物的肝脏和肾脏以及SD大鼠的这些相同器官和肿瘤（Walker 256腺癌）中进行了生物分布研究。获得的结果表明，除了这些组织中的DNA铂化外，大量的铂还掺入染色体蛋白（CP）和胞质组分中。当以注射药物总量的分数百分比（%ID/g）测定时，铂在胞质组分中的定位在肾脏中最高，其次是肿瘤，在肝脏中最低。目前尚不清楚铂在胞质和CP中的这种定位的意义，但它们可能参与顺铂的细胞毒性作用，因为这种药物对肿瘤和肾脏具有细胞毒性，但对肝脏没有细胞毒性。顺铂在肝脏、肾脏和肿瘤亚细胞组分中的定位显示，静脉输注后比静脉推注给药后有更高的趋势。
