cis- and trans-Diamminedichloroplatinum(II)-mediated cross-linking of chromosomal non-histone proteins to DNA in HeLa cells.

The cross-linking of chromosomal non-histone proteins to DNA in isolated nuclei or intact HeLa cells exposed to different concentrations of cis- and trans-diamminedichloroplatinum(II) (cis- and trans-DDP) for various time intervals was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical methods. Both the cis- and the trans-DDP cross-linked significant numbers of chromosomal non-histone proteins to the DNA. The quantity and the types of the cross-linked proteins depended on the time of incubation as well as on the concentrations of the drugs. The immunochemical techniques revealed that both the 0.35 M sodium chloride insoluble and soluble chromosomal non-histone proteins were cross-linked to the DNA by both isomers. The action of cis- and trans-DDP was reversed and/or blocked by thiourea or 2-mercaptoethanol. Pretreatment of isolated nuclei or chromatin with iodoacetamide or N-ethylmaleimide did not prevent the DNA-protein cross-linking.