It can be postulated that among the factors implicated in cartilaginous lesions, oxygen-derived free radicals seem to have a prominent part. To investigate this hypothesis, rabbit articular chondrocyte cultures have been exposed to oxygen-derived reactive species generated by the hypoxanthine-xanthine oxydase system. We observed a dose-dependent decrease of cellular growth. In order to explain this result, cell cycle progression and binucleate cell fractions have been studied. A greater number of binucleate cells and an increase in cell volume were observed. Flow cytometry analysis revealed a perturbation in cell cycle progression leading to a significant increase in the proportion of cells in G2 phase and an important augmentation in cell protein content confirmed by biochemical assays. This model shows which type of alteration can be induced by oxygen-derived free radicals in vitro. In addition, we deem this model to be useful for studying degenerative processes and for screening drugs that can scavenge oxygen-free radicals.

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The potentiation or antagonistic effects of Cu, Hg, Pb and Cd salts in the presence of a long-acting anti-rheumatic drug, D-penicillamine (D.P.) were studied on cultured chondrocytes. CuSO(4) (10(-4)M), HgCl(2) (10(-5)M), Pb(CH(3)COO)(2) (10(-3)M) and D.P. (10(-3)M) when used alone caused a small decrease in cell proliferation. The addition of D.P. with Cu, Hg or Pb salts resulted in a marked increase in the extent of growth inhibition. In contrast, CdCl(2) (10(-5)M) produced an important growth inhibitory effect, and D.P. antagonized CdCl(2) action. The CuSO(4) D.P. toxicity was probably due to production of H(2)O(2) in situ. To verify this hypothesis, catalase, responsible for H(2)O(2) metabolism was used, and was found to partially reverse the inhibitory effect of CuSO(4)-D.P.