In vivo DNA-protein cross-linking by cis- and trans-diamminedichloroplatinum(II)

When Novikoff hepatoma-bearing rats were given injections of a therapeutic dose of cis-diamminedichloroplatinum(II) (cis-DDP) (7 mg/kg), DNA-protein cross-links could be detected by using antisera to dehistonized chromatin, nuclear matrix, or Novikoff hepatoma cytoskeletal preparation. The extent of cross-linking increased in time up to 24 h after the injection, after which time the DNA-protein cross-links were gradually repaired, with no cross-links detectable at 72 h. trans-DDP in equitoxic (40 mg/kg) dose was very efficient in forming DNA-protein cross-links. Although formed more rapidly, these trans-DDP-mediated cross-links were repaired faster, within 48 h after the injection. The repair of cross-links at equimolar trans-DDP dose (7 mg/kg) was even more rapid. The principal proteins cross-linked to the DNA by both cis- or trans-DDP were Novikoff hepatoma cytokeratins (Mr 39,000, 49,000, 56,000, and an additional protein band reacting with the antiserum to Novikoff hepatoma cytoskeletal preparation at Mr approximately 68,000).