Modulation of cell and DNA damage by poly(ADP)ribose polymerase in lung cells exposed to H2O2 or asbestos fibres

Poly(ADP)ribose polymerase (PARP) may participate in cell survival, apoptos is and development of DNA damage. We investigated the role of PARP in trans formed human pleural mesothelial (MeT-SA) and alveolar epithelial (A549) ce lls exposed from 0.05 to 5 mM hydrogen peroxide (H2O2) or crocidolite asbes tos fibres (1-10 mu g/cm(2)) in the presence and absence of 3-aminobenzamid e (ABA), a PARP inhibitor. The cells were investigated for the development of cell injury, DNA single strand breaks and depletion of the cellular high -energy nucleotides. Compared to H2O2, fibres caused a minor decrease in ce ll viability and effect on the cellular high-energy nucleotide depletion, a nd a marginal effect on the development of DNA strand breaks when assessed by the single cell gel electrophoresis (the Comet assay). Inhibition of PAR P transiently protected the cells against acute H2O2 related irreversible c ell injury when assessed by microculture tetrazolium dye (XTT) assay and po tentiated oxidant related DNA damage when assessed by the Comet assay. Howe ver, PARP inhibition had no significant effect on fibre-induced cell or DNA toxicity with the exception of one fibre concentration (2 mu g/cm(2)) in M eT-SA cells. Apoptosis is often associated with PARP cleavage and caspase a ctivation. Fibres did not cause PARP cleavage or activation of caspase 3 fu rther confirming previous results about relatively low apoptotic potential of asbestos fibres. In conclusion, maintenance of cellular high-energy nucl eotide pool and high viability of asbestos exposed cells may contribute to the survival and malignant conversion of lung cells exposed to the fibres. (C) 2000 Elsevier Science B.V. All rights reserved.