Cytogenetic and oxidative damage induced in human lymphocytes by platinum, rhodium and palladium compounds.
This study of soluble compounds of platinum, palladium and rhodium investigated the genotoxic properties of (NH(4))(2)PtCl(4), PtCl(2), PtCl(4), (NH(4))(2)PdCl(4), PdCl(2) and RhCl(3) using the human lymphocyte micronucleus (MN) assay coupled with fluorescence in situ hybridization (FISH). A pancentromeric DNA probe was used to detect both centromere-positive micronuclei (C+ MN) as well as centromere-negative micronuclei (C- MN). A modified alkaline single cell gel electrophoresis (SCGE) assay was used to evaluate the possible role of oxidative damage in genotoxicity of the Pt, Pd and Rh compounds tested. Two enzymes, endonuclease III and formamidopyrimidine glycosylase, were used to recognize and subsequently cut oxidized pyrimidines and purines, respectively. A significant induction of MN by Pt and Rh compounds was observed compared with controls, while (NH(4))(2)PdCl(4) and PdCl(2) displayed weak significant MN induction. The FISH technique revealed no significant difference in the frequency of C+ MN and C- MN for all compounds tested. These findings suggest that MN induction is due both to a clastogenic and an aneuploidogenic mechanism. SCGE detected an increase in the level of DNA oxidative damage for the Rh compound and for Pt(IV) which was also capable of inducing an increase in primary DNA damage at all the tested doses. This work highlights the stronger genotoxicity, likely mediated by oxidative damage induction, of Pt and Rh compounds compared with Pd salts.
Dipartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, via S. Giuseppe 22, 56126 Pisa, Italy. l.migliore@geog.unipi.it
Lucia
L
Migliore
Giada
G
Frenzilli
Claudia
C
Nesti
Salvador
S
Fortaner
Enrico
E
Sabbioni
D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage; D015342:DNA Probes; D043382:DNA-Formamidopyrimidine Glycosylase; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects* / Q000378:metabolism; D015162:Micronucleus Tests; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D018384:Oxidative Stress; D010165:Palladium / Q000494:pharmacology*; D017671:Platinum Compounds / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D012238:Rhodium / Q000494:pharmacology*
D015342:DNA Probes; D017671:Platinum Compounds; D011687:Purines; D011743:Pyrimidines; D010165:Palladium; D012238:Rhodium; D005090:Exodeoxyribonucleases; C020133:exodeoxyribonuclease III; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase