Evidence for lack of mitochondrial DNA repair following cis-dichlorodiammineplatinum treatment.
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.
Singh
G
G
OCF, Hamilton Regional Cancer Centre, Ontario, Canada.
Maniccia-Bozzo
E
E
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D004272:DNA, Mitochondrial; D002945:Cisplatin