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).
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D007633:Keratins / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D003432:Cross-Linking Reagents; D011506:Proteins; D007633:Keratins; D004247:DNA; D002945:Cisplatin