title: Preferential binding of cisplatin to mitochondrial DNA and suppression of ATP generation in human malignant melanoma cells.
abstract: Effects of cisplatin on mitochondria in human malignant melanoma from gingiva were investigated. Cisplatin bound about 50 times more to mitochondrial DNA than to chromosomal DNA. NADH-ubiquinone reductase was decreased 48 h after the administration to about 40% of the initial level, and cellular ATP level was also depressed at that time. A good correlation was observed between the energy status and NADH-ubiquinone reductase activity. These results suggest that the preferential binding of cisplatin to mitochondrial DNA results in the inhibition of NADH-ubiquinone reductase and consequently in the disturbance of ATP generation.
authors.affiliation: Department of Biochemistry, Mie University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: H
authors.initials: H
authors.lastname: Hibasami
authors.forename: S
authors.initials: S
authors.lastname: Maekawa
authors.forename: T
authors.initials: T
authors.lastname: Tagawa
authors.forename: K
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D004247:DNA; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D004259:DNA-Directed DNA Polymerase; D002945:Cisplatin