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Keywords:

  • DNA—protein cross-links;
  • platinum compounds;
  • lymphocytes

Abstract

Cis -diamminedichloroplatinum(II) (cis -DDP) is one of the most often used anticancer drugs. It is generally accepted that the antitumor activity of the drug results from its interactions with DNA. Trans -diamminedichloroplatinum(II) (trans -DDP) also binds to DNA effectively, but is clinically ineffective. In the present work the lymphocyte nuclear proteins that participate in DNA—protein cross-links induced by cis - and trans -DDP are investigated. In lymphocytes which are incubated without platinum compounds there are DNA-binding proteins in the range of 45–71kDa. It is shown that additional proteins of 28, 30, 34.5, 45 and 120kDa are cross-linked with DNA in lymphocytes after 2-h incubation with cis -DDP at concentrations of 0.1 and 0.5mM. Trans -DDP does not bind additional proteins to DNA after the same incubation time. Electrophoretic analysis shows that trans -DDP binds much more of the same nuclear proteins to DNA than cis -DDP after 12-h incubation. In this study a test for the identification of 34.5kDa protein is also undertaken. This protein appears in the samples obtained after 12-h incubation of lymphocytes with cis - and trans -DDP at 0.5 and 1mM, especially. The protein of 34.5kDa from cross-links induced by 1mM trans -DDP is recognized by antibodies against the protein of the same molecular weight from the nuclear matrix of the lymphocytes. The results obtained here are discussed in relation to the biological activity of diamminedichloroplatinum isomers.