ABSTRACT
The objective of this study was to determine if the nephrotoxic effects induced by cisplatin were correlated to mitochondrial DNA damage. Comparisons were made with the liver since hepatotoxicity is rarely observed. Cisplatin doses of 10, 20 and 40 mg/kg were administered intraperitoneally to C57BL/6J mice. Mitochondrial DNA was isolated from both the hepatic and renal tissues and quantitated by hybridization with a specific mitochondrial probe. Cisplatin caused differential effects on mouse hepatic and renal mitochondrial DNA. The 10 and 20 mg/kg dose caused an elevation in mitochondrial DNA levels in the hepatic, but no increase in the renal tissue was observed. This is the first study demonstrating an organ specific effect of cisplatin at the DNA level.
Subject(s)
Cisplatin/pharmacology , DNA, Mitochondrial/metabolism , Kidney/metabolism , Liver/drug effects , Animals , Cisplatin/administration & dosage , Dose-Response Relationship, Drug , Kidney/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BLABSTRACT
The purpose of this study was to determine whether cis-dichlorodiammineplatinum (cisplatin) causes mitochondrial DNA (mtDNA) damage. A specific and sensitive method for quantitation of damage to mtDNA was used, by which the physical forms of mtDNA (supercoiled, open circular and linear forms) were separated by gel electrophoresis. The DNA specificity was then obtained by hybridizing with a mtDNA probe. In vitro incubation of mtDNA with cisplatin showed that the drug did not induce any changes in the proportion of physical forms; similar results were obtained in vivo. Since cisplatin did not cause any strand scission in mtDNA but induces strand breaks in nuclear DNA, which is an indirect effect, a lack of repair for cisplatin-induced adducts in mtDNA is suggested.
