Formation of DNA strand breaks by D-penicillamine and bucillamine in human lymphocytes

DNA strand breakage by D-penicillamine and bucillamine, anti-rheumatic agents with thiol residues was evaluated in DNA unwinding assays. When incubating human peripheral blood lymphocytes with D-penicillamine or bucillamine in the presence of 8 microM CuSO4, numerous DNA strand breaks occurred and those depended on the production of hydrogen peroxide and were completely blocked in the presence of catalase. This phenomenon was reversible, and fragmented DNA was repaired in 8 to 24 h. Significant decreases in cellular NAD levels were observed at concentrations of D-penicillamine or bucillamine which could damage DNA. As extensive depletion of cellular NAD functionally inactivates lymphocytes, the formation of DNA strand breaks may have a role in the immunomodulating action of these anti-rheumatic drugs.