Cisplatin generates superoxide anion by interaction with DNA in a cell-free system.
Cisplatin [cis-Diamminedichloroplatinum (II), DDP] generated superoxide anion (O2-), as measured by chemiluminescence from a Cypridina luciferin analog (CLA), by interaction with calf thymus DNA (ct-DNA) in phosphate-buffered saline (PBS) at pH 7.6. The intensity of chemiluminescence of CLA (CCLA) increased with increased concentration of DDP, ct-DNA or CLA in the limited range of concentrations of these agents tested. DDP-induced CCLA was completely inhibited by the addition of an O2- scavenger, superoxide dismutase (SOD), or an antioxidant, ascorbic acid. Heat-inactivated SOD did not affect CCLA. The hydroxyl radical (OH.) scavengers, mannitol, ethanol, and formic acid, also caused a partial suppression of CCLA, suggesting that DDP produced OH. as well as O2- in the cell-free system used.
Masuda
H
H
Department of Surgery, Kyushu Dental College, Japan.
Tanaka
T
T
Takahama
U
U
D000818:Animals; D000838:Anions; D002417:Cattle; D002474:Cell-Free System; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers; D006358:Hot Temperature; D017665:Hydroxyl Radical / Q000378:metabolism; D008163:Luminescent Measurements; D011719:Pyrazines / Q000378:metabolism / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D000838:Anions; D016166:Free Radical Scavengers; D011719:Pyrazines; C048193:2-methyl-6-phenyl-3,7-dihydroimidazo(1,2-a)pyrazin-3-one; D013481:Superoxides; D017665:Hydroxyl Radical; D004247:DNA; D013482:Superoxide Dismutase; D002945:Cisplatin