Cytotoxicity of D-penicillamine in association with several heavy metals against cultured rabbit articular chondrocytes.

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.