PALLADIUM OR PLATINUM EXACERBATES HYDROXYL RADICAL-MEDIATED DNA-DAMAGE

Strand breakage of supercoiled pBR322 DNA by a Fenton system is increa sed in the presence of palladium (Pd) or platinum (Pt) ions. Neither P d nor Pt ions can substitute for iron in the Fenton system. We have ob tained several lines of evidence that Pd and Pt ions in the presence o f a Fenton system can augment the production of OH., as monitored by a spectrophotometric method quantifying hydroxylated salicylate or by a fluorometric method quantifying catechol production. Furthermore, the promoting effect of both metal ions on OH. production was substantiat ed by the identification of multiple hydroxylated products of salicyla te [2,3-dihydroxybenzoate (A), 2,5-dihydroxybenzoate (B), and catechol (C)] using HPLC. The concentrations of A, B, and C produced in the co ntrol were 4.5, 8.0, and 2.0 mu M, respectively; whereas, their respec tive concentrations increased to 23.6, 42.0, and 10.0 mu M with the ad dition of Pd ions. The observed phenomenon was further confirmed by th e identification of HO-DMPO spin adducts using ESR spectroscopy. Taken together, our data suggest that the mechanism of Pd or Pt ion-mediate d exacerbation of DNA damage by a Fenton system is due to the promotio n of OH. production by these metal ions. (C) 1997 Elsevier Science Inc .