Mutagenesis, Vol. 17, No. 5, 411-417,
September 2002
© 2002 UK Environmental Mutagen Society/Oxford University Press
Cytogenetic and oxidative damage induced in human lymphocytes by platinum, rhodium and palladium compounds
Dipartimento di Scienze dell’Uomo e dell’Ambiente and 1 Dipartimento di Morfologia Umana e Biologia Applicata, University of Pisa, via S. Giuseppe 22, 56126 Pisa, Italy and 2 European Commission, JRC-Ispra, Institute for Health and Consumer Protection (IHCP), ECVAM Unit, 21020-Ispra, Varese, Italy
This study of soluble compounds of platinum, palladium and rhodium investigated the genotoxic properties of (NH4)2PtCl4, PtCl2, PtCl4, (NH4)2PdCl4, PdCl2 and RhCl3 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 (NH4)2PdCl4 and PdCl2 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.
3 To whom correspondence should be addressed. Tel: +39 050 836223; Fax: +39 050 551290; Email: l.migliore{at}geog.unipi.it
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